June 18, 2008, Vol 299, No. 23 >

< Previous Article Next Article >

Review | June 18, 2008 Clinician's Corner

Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk FREE

Alexander Thompson, MRes, MPhil; Emanuele Di Angelantonio, MD, MSc; Nadeem Sarwar, MRPharmS, MPhil; Sebhat Erqou, MD, MPhil; Danish Saleheen, MBBS, MPhil; Robin P. F. Dullaart, MD, PhD; Bernard Keavney, MD, FRCP; Zheng Ye, PhD; John Danesh, DPhil, FRCP

[+] Author Affiliations

Author Affiliations: Department of Public Health and Primary Care, University of Cambridge, Cambridge, England (Drs Di Angelantonio, Erqou, Saleheen, Ye, and Danesh, and Messrs Thompson and Sarwar); Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (Dr Dullaart); and Institute of Human Genetics, Newcastle University, Newcastle, England (Dr Keavney).

JAMA. 2008;299(23):2777-2788. doi:10.1001/jama.299.23.2777.

Text Size: A A A

Published online

Article

Figures

Tables

References

CME

ABSTRACT

Context The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk.

Objective To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk.

Data Sources Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators.

Study Selection Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and −629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], −631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms.

Data Extraction Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both.

Results Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113 833 healthy participants, and 46 studies had data on 27 196 coronary cases and 55 338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (−9.7%; 95% confidence interval [CI], −11.7% to −7.8%), lower mean CETP activity (−8.6%; 95% CI, −13.0% to −4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and −629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for −629C>A.

Conclusions Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.

Figures in this Article

Quiz Ref IDObservational and experimental studies in humans and animals have encouraged development of pharmacological agents that increase circulating levels of high-density lipoprotein cholesterol (HDL-C) in coronary disease prevention.¹^- 8 Such agents include inhibitors of cholesteryl ester transfer protein (CETP), a protein that facilitates exchange of cholesteryl esters for triglycerides between HDL and triglyceride-rich lipoproteins.⁵ One CETP inhibitor, torcetrapib, increases HDL-C levels by at least 60%,⁹ but produced an excess of deaths and cardiovascular events in the ILLUMINATE trial.¹⁰ Although the exact reasons for the failure of torcetrapib remain uncertain,¹¹^- 16 study of CETP genotypes may help to suggest whether further efforts to prevent coronary disease by CETP inhibition are warranted. Recent genome-wide association studies have reported that CETP genotypes are associated with HDL-C levels more strongly than any other loci across the genome.¹⁷^- 18 Furthermore, whereas the effect of a pharmacological agent on the CETP pathway may be difficult to disentangle from any “off-target” effects on other pathways, particular CETP genotypes should have more specific influences, notably on CETP mass and activity.

A previous meta-analysis¹⁹ of the association between CETP and coronary risk focused on only 1 CETP genotype in 10 studies involving a total of 13 677 participants, including 2857 coronary cases. The current reassessment of the associations of 6 CETP genotypes with CETP phenotypes, circulating lipid levels, and with coronary risk uses the following approaches to maximize power and minimize bias: (1) we report updated meta-analyses of CETP genotypes with CETP mass and activity, HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides, and apolipoproteins A-I and B (involving data on up to 113 833 participants in 92 studies); (2) we report updated meta-analyses of CETP genotypes with coronary outcomes (involving data on up to 27 196 coronary cases and 55 338 controls in 46 studies), with tabular data sought from investigators to supplement and update published data; (3) we contacted principal investigators of larger genetic association studies of variants other than CETP to seek unreported data; and (4) we compared the association between genetically mediated increases in HDL-C concentrations and coronary risk with those expected for equivalent increases in HDL-C concentrations in available prospective studies.

METHODS

Study Selection

We sought studies published between January 1970 and January 2008 on CETP genotype associations (GenBank accession number NM_000078) with CETP mass, CETP activity, concentrations of HDL-C, LDL-C, triglycerides, or apolipoproteins A-I and B, or with risk of myocardial infarction (generally defined by World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease [MONICA] criteria)²⁰ or angiographic coronary stenosis (generally defined as ≥50% of ≥ 1 major coronary arteries). For lipid markers, data were used from only apparently healthy individuals (ie, people without known coronary or other diseases or clinical lipid abnormalities) who had information on at least 1 relevant genotype. Electronic searches, not limited to the English language, were performed by using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database, and supplemented by scanning reference lists of articles identified for all relevant studies and review articles (including meta-analyses), by hand searching of relevant journals, and by correspondence with authors of included studies. The computer-based searches combined search terms related to CETP genotype (eg, cholesteryl ester transfer protein, cholesterol ester transfer protein, CETP, gene, genes, loci, polymorphi*, allel*, phenotyp*, SNP*, RFLP*, chromosom*, variant, mutat*), lipid phenotypes (eg, HDL, LDL, triglycerides, apolipoproteins), and coronary disease (eg, myocardial infarction, atherosclerosis, coronary heart disease, coronary stenosis) without language restriction (Figure 1).

Place holder to copy figure label and caption

Figure 1. Study Flow Diagram

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

CETP indicates cholesteryl ester transfer protein.
^aBecause these studies tended to be smaller, they comprised a total of only approximately 3% of the overall number of coronary cases included in this review, and a total of only approximately 8% of the overall number of participants included in the analysis of lipid concentrations.

Data Extraction

Information was recorded on TaqIB (rs708272), I405V (rs5882), −629C>A (rs1800775), D442G (rs2303790), −631C>A (rs1800776), and R451Q (rs1800777). The following data were extracted independently by 3 investigators (S.E., D.S., and Z.Y.), using a protocol previously described²¹: genotype frequencies by categorical disease outcome; means and standard deviations of lipid markers by genotype; mean age of cases; proportions of men and ethnic subgroups (defined as people of white European continental ancestry, East Asian, or other [South Asian, Middle Eastern, South American, and North African]); and fasting status and assay methods. Discrepancies were resolved by discussion and by adjudication of a fourth reviewer (A.T.). We used the most up-to-date information in cases of multiple publications. We supplemented published data by a tabular data request to (1) authors of published reports, (2) investigators of 75 potentially relevant unreported studies involving at least 500 coronary cases or at least 1000 healthy participants listed in published meta-analyses²¹^- 25 of variants other than CETP, and (3) authors of published genome-wide association studies of relevant outcomes.²⁶^- 27

Statistical Analysis

Analyses were performed by using only within-study comparisons to limit possible biases, involving studies that had used accepted genotyping and lipid assay methods and coronary outcomes (as described above). Principal analyses were prespecified to involve codominant genetic models. Summary odds ratios (ORs) for coronary disease and mean levels of lipid markers (and differences in mean levels in comparison with the common homozygotes) were calculated by using a random-effects model that included between-study heterogeneity (with sensitivity analyses involving fixed-effect models). To enable comparison of the magnitude of any associations with several different lipid markers and CETP phenotypes, associations were also presented as per-allele percentage differences (calculated in reference to the weighted mean level of each marker in common homozygotes). For studies that compared a single control group with both myocardial infarction and (nonoverlapping) coronary stenosis cases, we avoided any double counting by analyzing myocardial infarction and coronary stenosis cases separately before combining them into a single coronary disease group. Consistency of findings across studies was assessed by using the I² statistic.²⁸ Heterogeneity was assessed by using the Q statistic and by examining prespecified groupings of study characteristics. Evidence of publication bias was assessed by using funnel plots, the Egger test,²⁹ and by comparing pooled results from studies involving at least 500 coronary cases (or ≥1000 healthy participants for gene-lipid investigations) with pooled results from smaller studies. Evidence of deviation from Hardy-Weinberg equilibrium was assessed by χ² tests using the genotype frequencies in healthy individuals, with sensitivity analyses involving significance levels of both P < .05 and P < .01. Coronary heart disease risk estimates from the Prospective Studies Collaboration¹ were used to calculate expected ORs for coronary disease corresponding to the per-allele increases in HDL-C levels observed with the CETP genotypes in this review, involving a χ² test for consistency of genotype-coronary risk associations with HDL-C coronary risk associations. All analyses were performed by using Stata release 10 (StataCorp LP, College Station, Texas). All statistical tests were 2-sided and used a significance level of P < .05, except where indicated.

RESULTS

A total of 102 relevant studies reporting on 147 599 individuals were identified, including 38 studies that provided supplementary or previously unreported tabular data (Figure 1, eTable 1, and eTable 2).¹⁷^,30^- 165 Forty-five studies were based in Europe, 15 in North America, 29 in East Asia (predominantly China and Japan), 11 in other regions, and 2 studies were multinational. Twenty-one studies were prospective in design and 81 were either cross-sectional or case-control. The minor allele frequency in healthy white individuals was 0.42 for TaqIB (rs708272), 0.35 for I405V (rs5882), 0.48 for −629C>A (rs1800775), less than 0.01 for D442G (rs2303790), 0.08 for −631C>A (rs1800776), and 0.04 for R451Q (rs1800777) (Table 1). Previous studies have reported almost complete linkage of TaqIB with −629C>A, but the other CETP genotypes considered in this review appear to be only weakly correlated.¹⁶⁶

Table 1. Description of CETP Genotypes Included in the Review

View Large | Save Table | Download Slide (.ppt) | View in Article Context

CETP Phenotypes and Lipid Levels

Ninety-two studies of CETP genotypes involving 113 833 individuals were identified that reported on CETP mass, CETP activity, circulating lipid levels, or all 3,¹⁷^,30^- 148 including 36 studies that provided supplementary or previously unreported data on 49 502 individuals (Table 2). Of 91 studies assessing associations with HDL-C, 7 used homogeneous assay methods to measure HDL-C levels, 49 used nonhomogeneous methods, and 35 did not report the assay method used. Overall, for each A allele inherited, carriers of the TaqIB variant had lower mean CETP mass (−9.7%; 95% confidence interval [CI], −11.7% to −7.8%), lower mean CETP activity (−8.6%; 95% CI, −13.0% to −4.1%), higher mean HDL-C levels (4.5%; 95% CI, 3.8%-5.2%), higher mean apolipoprotein A-I levels (2.4%; 95% CI, 1.6%-3.2%), lower mean LDL-C levels (−0.9%; 95% CI, −1.6% to −0.3%), lower mean apolipoprotein B levels (−0.5%; 95% CI, −1.1% to 0.1%), and lower mean triglycerides (−2.0%; 95% CI, −3.2% to −0.7%) than did common homozygotes (Figure 2). Overall, per G allele inherited, carriers of the I405V variant had lower mean CETP mass (−5.7%; 95% CI, −7.5% to −4.0%), lower mean CETP activity (−8.2%; 95% CI, −17.8% to 1.3%), higher mean HDL-C levels (2.5%; 95% CI, 1.8%-3.2%), higher mean apolipoprotein A-I levels (1.6%; 95% CI, 1.2%-2.0%), and lower mean triglycerides (−2.1%; 95% CI, −3.0% to −1.1%) than did common homozygotes but no discernible differences in LDL-C or apolipoprotein B levels. Overall, per A allele inherited, carriers of the −629C>A variant had lower mean CETP mass (−9.4%; 95% CI, −13.8% to −5.0%), lower mean CETP activity (−5.9%; 95% CI, −11.0% to −0.8%), higher mean HDL-C levels (4.9%; 95% CI, 4.3%-5.4%), higher mean apolipoprotein A-I levels (1.8%; 95% CI, 0.7%-2.8%), and lower mean triglycerides (−2.1%; 95% CI, −3.4% to −0.9%) than did common homozygotes but no discernible differences in LDL-C or apolipoprotein B levels. Data were insufficient for informative per-allele estimates in relation to D442G, −631C>A, and R451Q (Table 2); however, in dominant models, they were associated with mean differences in HDL-C of 13.4% (95% CI, 9.4%-17.4%), −0.7% (95% CI, −2.4% to 1.0%), and −8.8% (95% CI, −9.7% to −7.9%), respectively, compared with common homozygotes.

Table 2. Summary of Data Available on CETP Genotypes, CETP Phenotypes, Lipid Levels, and Coronary Outcomes^a

View Large | Save Table | Download Slide (.ppt) | View in Article Context

Place holder to copy figure label and caption

Figure 2. Associations of CETP Genotypes With CETP Phenotypes and Lipid Levels

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

CETP indicates cholesteryl ester transfer protein; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. To convert apolipoproteins A-I and B to mg/dL, divide by 0.01; to convert HDL-C and LDL-C to mg/dL, divide by 0.0259; and to convert triglyercides to mg/dL, divide by 0.0113. Assessment of heterogeneity: I² (95% CI) for CETP mass, CETP activity, HDL-C, apolipoprotein A-I, LDL-C, apolipoprotein B, and triglycerides, respectively, were 66% (39%-81%), 71% (44%-86%), 75% (69%-80%), 66% (46%-78%), 51% (32%-65%), 14% (0%-51%), and 49% (30%-62%) for TaqIB; 0% (0%-71%), NA*, 56% (33%-71%), 0% (0%-68%), 24% (0%-58%), 16% (0%-60%), and 0% (0%-49%) for I405V; and 71% (17%-90%), NA*, 37% (0%-61%), 36% (0%-78%), 29% (0%-63%), 0% (0%-90%), and 0% (0%-57%) for −629C>A. NA* indicates I² statistics were not calculated when there were only 2 studies.
^aPooled estimates calculated by random-effects models. Estimates calculated by fixed-effect models are shown in eTable 3.
^bStandardized mean differences.
^cCalculated with reference to the weighted mean level of each marker in common homozygotes.

There was evidence of heterogeneity in associations with HDL-C across studies (TaqIB: I² = 75%; 95% CI, 69%-80%; I405V: I² = 56%; 95% CI, 33%-71%; −629C>A: I² = 37%; 95% CI, 0%-61%). This heterogeneity was partly explained by study level characteristics that had been recorded, including population source (TaqIB and −629C>A), ethnicity (TaqIB and −629C>A), study size (I405V), and whether data were obtained through correspondence with investigators or were extracted directly from published reports (TaqIB) (Figure 3). Significant deviation from Hardy-Weinberg equilibrium (P < .05) was detected in 10 studies for TaqIB (including 5 studies at P < .01), 2 studies for I405V (both studies at P < .01), and 4 studies for −629C>A (including 2 studies at P < .01), but their exclusion did not materially change the findings. Analyses by study size (Figure 3) and other standard tests (eFigure) did not reveal strong evidence of publication bias.

Place holder to copy figure label and caption

Figure 3. Mean Differences in HDL-C Levels Associated With CETP Genotypes, Grouped by Recorded Study Characteristics

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

CETP indicates cholesteryl ester transfer protein; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol. To convert HDL-C to mg/dL, divide by 0.0259. Sizes of data markers are proportional to the inverse of the variance of the weighted mean difference. For sex and ethnicity, studies may have contributed data to more than 1 category. Overall estimates were calculated using random-effects models (fixed-effect estimates are provided in eTable 3). Several recorded characteristics explained part of the heterogeneity observed, including ethnicity (P = .008), population source (P = .04), and data source (P < .001) for TaqIB; study size (P = .02) for I405V; and ethnicity (P < .001) and population source (P = .007) for −629C>A.

Coronary Outcomes

Forty-six studies reported data on 27 196 coronary cases and 55 338 controls,³⁰^- 35,39^,42^- 45,51^- 53,59^,61^,63^- 68,71^,78^- 81,85^- 87,90^,94^,98^- 100,103^,105^,107^- 111,113^- 115,117^- 123,133^,135^,138^- 140,142^- 143,145^- 148,150^- 165 including 21 studies that provided supplementary or previously unreported data on 17 187 cases and 38 619 controls. Thirty-three studies recruited controls from general populations, 11 studies recruited controls from hospitals or were based in clinical trials, and 2 studies used both sources. The combined OR for coronary disease was 0.95 (95% CI, 0.92-0.99) per A allele of the TaqIB variant. There was possible modest heterogeneity among the 38 available studies (I² = 18%; 95% CI, 0%-45%; P = .17), including somewhat more modest findings in the larger studies and those studies that had provided data through correspondence (P = .01 and P = .003, respectively, for heterogeneity) (Figure 4). The combined OR for coronary disease was 0.94 (95% CI, 0.89-1.00) per G allele of the I405V variant. There was possible modest heterogeneity among the 18 available studies (I² = 39%; 95% CI, 0%-66%; P = .04), with most of it accounted for by differences in the selection of control groups (P < .001). The combined OR for coronary disease was 0.95 (95% CI, 0.91-1.00) per A allele of the −629C>A variant. There was possible moderate heterogeneity among the 17 available studies (I² = 32%; 95% CI, 0%-62%; P = .10), but little of it was explained by the study characteristics recorded.

Place holder to copy figure label and caption

Figure 4. CETP Genotypes and Coronary Risk, Grouped by Recorded Study Characteristics

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

CETP indicates cholesteryl ester transfer protein; CI, confidence interval. Sizes of data markers are proportional to the inverse of the variance of the log_e odds ratio. For ethnicity, source of controls, and outcome assessed, studies may have contributed data to more than 1 category. For ethnicity, results are not presented for 4 studies of TaqIB and 2 studies of I405V and −629C>A that were predominantly based in nonwhite, non−East Asian individuals. For outcome assessed in TaqIB, results are not presented for 1 study that did not provide genotype frequencies separately for cases of myocardial infarction and coronary stenosis. Assessment of heterogeneity: TaqIB (I² = 18%; 95% CI, 0%-45%), I405V (I² = 39%; 95% CI, 0%-66%), or −629C>A (I² = 32%; 95% CI, 0%-62%). Observed heterogeneity could be partially explained by study size (P = .01) and data source (P = .003) for TaqIB and by source of controls (P < .001) for I405V (other comparisons P = .05 for each). Overall estimates were calculated using random-effects models; those calculated using fixed-effect models were 0.96 (95% CI, 0.93-0.99) for TaqIB, 0.95 (95% CI, 0.92-0.99) for I405V, and 0.95 (95% CI, 0.91-0.99) for −629C>A.

Significant deviation from Hardy-Weinberg equilibrium (P < .05) was detected in the controls of 6 studies for TaqIB (including 2 studies at P < .01), 1 study for I405V (P < .01), and 3 studies for −629C>A (including 1 study at P < .01). Again, exclusion of these studies did not materially change the findings. As was the case for studies of CETP phenotypes and lipid levels, there was not good evidence of publication bias from standard tests (eFigure), with the possible exception of TaqIB (Figure 4). Data were insufficient to provide informative risk estimates for the 3 rare CETP genotypes. Figure 5 displays estimates of associations between HDL-C and coronary risk derived from the Prospective Studies Collaboration,¹ providing a comparison of ORs for coronary disease per-allele increases in HDL-C in genetic studies vs those ORs in prospective studies of HDL-C (for TaqIB, 0.95; 95% CI, 0.92-0.99 vs 0.92; 95% CI, 0.91-0.93; P for heterogeneity = .11; for I405V, 0.94; 95% CI, 0.89-1.00 vs 0.95; 95% CI, 0.94-0.97; P = .72; and for −629C>A, 0.95; 95% CI, 0.91-1.00 vs 0.92; 95% CI, 0.91-0.93; P = .19).

Place holder to copy figure label and caption

Figure 5. Observed Per-Allele Odds Ratios for Coronary Disease With CETP Variants vs Odds Ratios Derived From Available Prospective Studies of HDL-C Levels

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

CETP indicates cholesteryl ester transfer protein; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol. Sizes of data markers are proportional to the inverse of the variance of the log_e risk estimate. χ² Test for difference: P = .11 for TaqIB, P = .72 for I405V, and P = .19 for −629C>A.
^aPer-allele odds ratio for coronary disease as shown in Figure 4.
^bHazard ratios for coronary heart disease calculated by using risk estimates from 153 798 participants in 61 studies¹ for an increase in usual HDL-C levels equal to those observed per allele for TaqIB, I405V, and −629C>A (Figure 2).

COMMENT

Quiz Ref IDStudy of CETP genotypes that alter CETP mass and activity can help to clarify the relevance of the CETP pathway to lipid metabolism and coronary disease risk. However, because particular CETP genotypes are only modestly associated with CETP phenotypes and lipid levels, reliable genetic studies may require many thousands of participants, including large numbers of patients with coronary disease. In the absence of very large individual studies, we have conducted an updated meta-analysis that involves a total of more than 147 000 individuals (including more than 27 000 coronary cases).Quiz Ref IDWe demonstrated that common CETP genotypes decrease CETP mass and activity by approximately 5% to 10%, increase HDL-C and apolipoprotein A-I by approximately 3% to 5% (which is comparable with the observed differences in HDL-C between smokers and nonsmokers), and decrease triglycerides by approximately 2%. Associations with LDL-C and apolipoprotein B were even smaller or negligible. Quiz Ref IDWe showed that the same CETP genotypes that are modestly associated with increased HDL-C levels are weakly and inversely associated with coronary risk. The magnitude of per-allele risk reductions were compatible with those expected on the basis of associations observed between HDL-C levels and coronary risk in prospective studies (Figure 5).¹ As discussed below, however, the quantity and quality of available genetic data require careful consideration.

Compared with a previous meta-analysis¹⁹ that focused solely on associations of the TaqIB variant with HDL-C levels and coronary disease risk, our review considers 6 CETP genotypes, assesses associations with several different lipid markers, and involves more than 10 times as much data. These data provide greater power than previously available to quantify the magnitude of any associations and, by including a considerable amount of previously unreported data, should reduce the scope for publication bias.²¹ However, although we did not detect strong evidence of selective publication, it is difficult to discount such bias entirely, particularly given the weak associations observed, the reliance of these associations on pooling results from both larger and smaller studies, and the general insensitivity of statistical tests for publication bias. (Ideally, with the availability of even larger numbers, pooled analyses would involve data from only the larger studies, which should be less liable to publication bias.) Because we did not have access to individual data, we could not control for population stratification,¹⁶⁷ conduct mendelian randomization analyses,¹⁶⁸^- 169 adjust for variables in possible intermediate pathways, explore heterogeneity by individual-level characteristics, or conduct haplotype analyses. These considerations highlight the need for very large individual studies of CETP genotypes with concomitant assessment of CETP phenotypes and lipid levels, perhaps involving more than 10 000 coronary cases and a similar number of controls. Quiz Ref IDFurthermore, large-scale studies with lifestyle data will be needed to explore potential joint effects of CETP genotypes with environmental determinants of HDL-C levels (eg, exercise and alcohol) on risk of coronary disease. Even larger such studies will be needed for reliable assessment of the less common CETP genotypes.¹⁷⁰

In contrast with available evidence from relatively short-term randomized trials of CETP inhibition,¹⁰^,14 our analyses suggest that individuals with (presumably lifelong) increased HDL-C levels as a result of genetically mediated reductions in CETP may be at slightly reduced coronary risk. This apparent discrepancy may relate to “off-target” effects potentially specific to torcetrapib (notably interference with the renin-angiotensin system and blood pressure elevation).¹⁰ On the other hand, it has been suggested that HDL particles produced under conditions of CETP inhibition may be dysfunctional, with any apparent increase in HDL-C levels offset by compensatory HDL-C clearance through direct hepatic pathways¹¹ and reduced apolipoprotein A-I–mediated removal of intracellular-free cholesterol from macrophages.¹¹^- 12 Further trials of other CETP inhibitors¹⁷¹ and investigations of CETP genotypes in relation to blood pressure and other traits may help to address such mechanistic concerns.

CONCLUSION

In summary, 3 CETP genotypes are associated with moderate inhibition of CETP activity, modestly higher HDL-C levels, and weakly inverse associations with coronary risk. This study illustrates the need for larger studies to demonstrate the modest impact that single genetic variants have on complex outcomes such as coronary disease. Further studies are warranted to determine the value of CETP inhibition to coronary disease prevention.

AUTHOR INFORMATION

Corresponding Author: John Danesh, DPhil, FRCP, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, England CB1 8RN (john.danesh@phpc.cam.ac.uk).

Author Contributions: Dr Danesh and Mr Thompson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Thompson, Di Angelantonio, Sarwar, Dullaart, Ye, Danesh.

Acquisition of data: Thompson, Di Angelantonio, Sarwar, Erqou, Saleheen, Dullaart, Ye, Danesh.

Analysis and interpretation of data: Thompson, Di Angelantonio, Sarwar, Erqou, Keavney, Ye, Danesh.

Drafting of the manuscript: Thompson, Di Angelantonio, Sarwar, Danesh.

Critical revision of the manuscript for important intellectual content: Thompson, Di Angelantonio, Sarwar, Erqou, Saleheen, Dullaart, Keavney, Ye, Danesh.

Statistical analysis: Thompson, Di Angelantonio, Sarwar, Erqou.

Obtained funding: Danesh.

Administrative, technical, or material support: Thompson, Di Angelantonio, Erqou, Saleheen, Dullaart, Ye, Danesh.

Study supervision: Danesh.

Drs Di Angelantonio and Erqou, and Messrs Thompson and Sarwar contributed equally to this article and are considered joint first authors.

Financial Disclosures: None reported.

Funding/Support: This work was supported by a British Heart Foundation program grant. Dr Danesh has been supported by the Raymond and Beverly Sackler Award in the Medical Sciences. Dr Di Angelantonio and Mr Thompson are supported by, and Mr Sarwar was supported by, a UK Medical Research Council PhD studentship. Dr Erqou is supported by a Gates Cambridge Scholarship and the UK Overseas Research Trust. Dr Saleheen is supported by the Yousef Jameel Foundation. Aspects of this work have been supported by an unrestricted educational grant from GlaxoSmithKline.

Role of the Sponsors: The sponsors had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Additional Contributions: Rory Collins, FMedSci, FRCP (University of Oxford, Oxford, England), commented helpfully. Angela Harper (University of Cambridge, Cambridge, England) provided administrative support. The following investigators kindly provided additional information from their studies: Birgit Agerholm-Larsen, MSc, PhD, Herlev University Hospital, Herlev, Denmark; Nassr Al-Daghri, MD, Birmingham Heartlands Hospital, Birmingham, England; Rolf V. Andersen, MSc, PhD, Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark; Yasumichi Arai, PhD, Keio University School of Medicine, Tokyo, Japan; Gil Atzmon, PhD, Albert Einstein College of Medicine, New York, New York; Nir Barzilai, MD, Albert Einstein College of Medicine, New York, New York; Anja Bauerfeind, PhD, Humboldt University of Berlin, Berlin, Germany; Susanna E. Borggreve, MD, University Medical Center Groningen, Groningen, the Netherlands; Michiel L. Bots, MD, PhD, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands; Hannia Campos, PhD, Harvard School of Public Health, Boston, Massachusetts; Peter Clifton, MD, PhD, CSIRO Human Nutrition, Adelaide, Australia; Eliana C. de Faria, MD, MS, PhD, State University of Campinas, Sao Paulo, Brazil; Robin P. F. Dullaart (on behalf of the PREVEND Study Group), MD, PhD, University Medical Center Groningen, Groningen, the Netherlands; Moses Elisaf, MD, University of Ioannina, Ioannina, Greece; Jeanette Erdmann, PhD, Medizinische Klinik II, Lübeck University, Lübeck, Germany; Dilys Freeman, PhD, University of Glasgow, Glasgow, Scotland; Domenico Girelli, MD, PhD, University of Verona, Verona, Italy; Akitomo Goto, MD, Nagoya City University, Nagoya, Japan; John Griffin, PhD, The Scripps Research Institute, La Jolla, California; Wendy Hall, PhD, King's College, London, England; Mohamed Hammami, MD, Monastir University, Monastir, Tunisia; A. Geert Heidema, MSc, University of Maastricht, Maastricht, the Netherlands; Benjamin D. Horne (on behalf of the Intermountain Heart Collaborative Study Group), PhD, MPH, Intermountain Medical Center, Murray, Utah; Akihiro Inazu, MD, PhD, Kanazawa University, Kanazawa, Japan; Aaron Isaacs, DSc, Genetic Epidemiology Unit, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Turgay Isbir, MD, University of Istanbul, Istanbul, Turkey; Yangsoo Jang, MD, PhD, Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, South Korea; Majken K. Jensen, MSc, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Bernard Keavney, MD, FRCP (on behalf of the ISIS Collaborative Group), Newcastle University, Newcastle, England; Kathy Klos, PhD, University of Texas–Houston Health Science Center, Houston, Texas; Jong Ho Lee, PhD, Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, South Korea; Robert W. Mahley, MD, PhD, University of California, San Francisco; Massimo Mangino, PhD, University of Leicester, Leicester, England; Nicola Martinelli, MD, University of Verona, Verona, Italy; Pamela McCaskie, BSc(Hons), University of Western Australia, Perth, Australia; Manjari Mukherjee, MD, India N.H. Hospital, Bangalore, India; Børge G. Nordestgaard, MD, DMSc, Herlev University Hospital, Herlev, Denmark; Kenji Okumura, MD, Nagoya University School of Medicine, Nagoya, Japan; Oliviero Olivieri, MD, University of Verona, Verona, Italy; Natalie Pecheniuk, PhD, The Scripps Research Institute, La Jolla, California; Jogchum Plat, PhD, Maastricht University, Maastricht, the Netherlands; Qin Qin, MD, Tianjin Chest Hospital, Tianjin, China; Eric B. Rimm, ScD, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Nilesh Samani, MD, FRCP, University of Leicester, Leicester, England; José V. Sorli, MD, University of Valencia, Valencia, Spain; John F. Thompson, PhD, Pfizer Global Research and Development, Groton, Connecticut; Martin Tobin, PhD, University of Leicester, Leicester, England; Anne Tybjærg-Hansen, MD, DMSc, Copenhagen University Hospital, Copenhagen, Denmark; Yvonne van der Schouw, PhD, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands; Cornelia M. van Duijn, PhD, Genetic Epidemiology Unit, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Mitsuhiro Yokota, MD, PhD, FACC, Aichi-Gakuin University, Nagoya, Japan; Shinji Yokoyama, MD, PhD, FRCPC, Nagoya City University, Nagoya, Japan; Mohammad Hadi Zafarmand, MD, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands; Guo-Bing Zhang, MD, Shanghai First People’s Hospital, Shanghai, China. None of these individuals received any compensation.

REFERENCES

Prospective Studies Collaboration. Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370(9602):1829-1839
PubMed | Link to Article

Packard C. A triumvirate of targets in the prevention and treatment paradigm for cardiovascular disease. Atheroscler Suppl. 2006;7(1):21-29
PubMed | Link to Article

Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA. 2007;298(7):786-798
PubMed | Link to Article

Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297(5):499-508
PubMed | Link to Article

Hamilton JA, Deckelbaum RJ. Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? Nat Struct Mol Biol. 2007;14(2):95-97
PubMed | Link to Article

Packard C, Nunn A, Hobbs R. High-density lipoprotein: guardian of the vascular system? Int J Clin Pract. 2002;56(10):761-771
PubMed

Inazu A, Brown ML, Hesler CB, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990;323(18):1234-1238
PubMed | Link to Article

Okamoto H, Yonemori F, Wakitani K, et al. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature. 2000;406(6792):203-207
PubMed | Link to Article

Clark RW, Sutfin TA, Ruggeri RB, et al. Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler Thromb Vasc Biol. 2004;24(3):490-497
PubMed | Link to Article

Barter PJ, Caulfield M, Eriksson M, et al; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109-2122
PubMed | Link to Article

Tall AR. CETP inhibitors to increase HDL cholesterol levels. N Engl J Med. 2007;356(13):1364-1366
PubMed | Link to Article

Tall AR, Yvan-Charvet L, Wang N. The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol. 2007;27(2):257-260
PubMed | Link to Article

Dullaart RP, Dallinga-Thie GM, Wolffenbuttel BH, van Tol A. CETP inhibition in cardiovascular risk management: a critical appraisal. Eur J Clin Invest. 2007;37(2):90-98
PubMed | Link to Article

Bots ML, Visseren FL, Evans GW, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet. 2007;370(9582):153-160
PubMed | Link to Article

Mazzone T. HDL cholesterol and atherosclerosis. Lancet. 2007;370(9582):107-108
PubMed | Link to Article

Rader DJ. Illuminating HDL: is it still a viable therapeutic target? N Engl J Med. 2007;357(21):2180-2183
PubMed | Link to Article

Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40(2):189-197
PubMed | Link to Article

Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40(2):161-169
PubMed | Link to Article

Boekholdt SM, Sacks FM, Jukema JW, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111(3):278-287
PubMed | Link to Article

Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project: registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation. 1994;90(1):583-612
PubMed

Bennet AM, Di Angelantonio E, Ye Z, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007;298(11):1300-1311
PubMed | Link to Article

Casas JP, Cavalleri GL, Bautista LE, et al. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am J Epidemiol. 2006;164(10):921-935
PubMed | Link to Article

Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ. 2005;331(7524):1053
PubMed | Link to Article

Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet. 2004;363(9410):689-695
PubMed | Link to Article

Ye Z, Liu EH, Higgins JP, et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet. 2006;367(9511):651-658
PubMed | Link to Article

Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443-453
PubMed | Link to Article

Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661-678
PubMed | Link to Article

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560
PubMed | Link to Article

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634
PubMed | Link to Article

Thompson JF, Wood LS, Pickering EH, Dechairo B, Hyde CL. High-density genotyping and functional SNP localization in the CETP gene. J Lipid Res. 2007;48(2):434-443
PubMed | Link to Article

Thompson JF, Durham LK, Lira ME, Shear C, Milos PM. CETP polymorphisms associated with HDL cholesterol may differ from those associated with cardiovascular disease. Atherosclerosis. 2005;181(1):45-53
PubMed | Link to Article

Lloyd DB, Lira ME, Wood LS, et al. Cholesteryl ester transfer protein variants have differential stability but uniform inhibition by torcetrapib. J Biol Chem. 2005;280(15):14918-14922
PubMed | Link to Article

Hinds DA, Seymour AB, Durham LK, et al. Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels. Hum Genomics. 2004;1(6):421-434
PubMed

Lira ME, Lloyd DB, Hallowell S, Milos PM, Thompson JF. Highly polymorphic repeat region in the CETP promoter induces unusual DNA structure. Biochim Biophys Acta. 2004;1684(1-3):38-45
PubMed

Thompson JF, Lloyd DB, Lira ME, Milos PM. Cholesteryl ester transfer protein promoter single-nucleotide polymorphisms in Sp1-binding sites affect transcription and are associated with high-density lipoprotein cholesterol. Clin Genet. 2004;66(3):223-228
PubMed | Link to Article

Akita H, Chiba H, Tsuchihashi K, et al. Cholesteryl ester transfer protein gene: two common mutations and their effect on plasma high-density lipoprotein cholesterol content. J Clin Endocrinol Metab. 1994;79(6):1615-1618
PubMed | Link to Article

Al-Daghri NM, Al-Attas O, Patel A, et al. Association between the cholesteryl ester transfer protein TaqI-detectable B polymorphism and low high-density lipoprotein cholesterol concentration in Saudis. Clin Sci (Lond). 2003;105(4):467-472
PubMed | Link to Article

Arai Y, Hirose N, Yamamura K, et al. Deficiency of choresteryl ester transfer protein and gene polymorphisms of lipoprotein lipase and hepatic lipase are not associated with longevity. J Mol Med. 2003;81(2):102-109
PubMed

Arca M, Montali A, Ombres D, et al. Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis. Clin Genet. 2001;60(5):374-380
PubMed | Link to Article

Volcik K, Ballantyne CM, Pownall HJ, Sharrett AR, Boerwinkle E. Interaction effects of high-density lipoprotein metabolism gene variation and alcohol consumption on coronary heart disease risk: the atherosclerosis risk in communities study. J Stud Alcohol Drugs. 2007;68(4):485-492
PubMed

Nettleton JA, Steffen LM, Ballantyne CM, Boerwinkle E, Folsom AR. Associations between HDL-cholesterol and polymorphisms in hepatic lipase and lipoprotein lipase genes are modified by dietary fat intake in African American and white adults. Atherosclerosis. 2007;194(2):e131-e140
PubMed | Link to Article

Blankenberg S, Tiret L, Bickel C, et al. Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease: the AtheroGene case control study [in German]. Z Kardiol. 2004;93(suppl 4) IV16-IV23
PubMed | Link to Article

Barzilai N, Atzmon G, Derby CA, Bauman JM, Lipton RB. A genotype of exceptional longevity is associated with preservation of cognitive function. Neurology. 2006;67(12):2170-2175
PubMed | Link to Article

Barzilai N, Atzmon G, Schechter C, et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA. 2003;290(15):2030-2040
PubMed | Link to Article

Bergman A, Atzmon G, Ye K, MacCarthy T, Barzilai N. Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol. 2007;3(8):e170
PubMed | Link to Article

Bauerfeind A, Knoblauch H, Schuster H, Luft FC, Reich JG. Single nucleotide polymorphism haplotypes in the cholesteryl-ester transfer protein (CETP) gene and lipid phenotypes. Hum Hered. 2002;54(4):166-173
PubMed | Link to Article

Bauerfeind A, Knoblauch H, Costanza MC, et al. Concordant association of lipid gene variation with a combined HDL/LDL-cholesterol phenotype in two European populations. Hum Hered. 2006;61(3):123-131
PubMed | Link to Article

Bernstein MS, Costanza MC, James RW, et al. No physical activity x CETP 1b.-629 interaction effects on lipid profile. Med Sci Sports Exerc. 2003;35(7):1124-1129
PubMed | Link to Article

Klos KL, Sing CF, Boerwinkle E, et al. Consistent effects of genes involved in reverse cholesterol transport on plasma lipid and apolipoprotein levels in CARDIA participants. Arterioscler Thromb Vasc Biol. 2006;26(8):1828-1836
PubMed | Link to Article

Carr MC, Ayyobi AF, Murdoch SJ, Deeb SS, Brunzell JD. Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein to LDL and HDL heterogeneity in healthy women. Arterioscler Thromb Vasc Biol. 2002;22(4):667-673
PubMed | Link to Article

Agerholm-Larsen B, Tybjaerg-Hansen A, Schnohr P, Steffensen R, Nordestgaard BG. Common cholesteryl ester transfer protein mutations, decreased HDL cholesterol, and possible decreased risk of ischemic heart disease: the Copenhagen City Heart Study. Circulation. 2000;102(18):2197-2203
PubMed

Agerholm-Larsen B, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A. Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene. Circulation. 2000;101(16):1907-1912
PubMed

Heidema AG, Feskens EJ, Doevendans PA, et al. Analysis of multiple SNPs in genetic association studies: comparison of three multi-locus methods to prioritize and select SNPs. Genet Epidemiol. 2007;31(8):910-921
PubMed | Link to Article

Boer JM, Feskens EJ, Kuivenhoven JA, et al. Parental history of myocardial infarction: lipid traits, gene polymorphisms and lifestyle. Atherosclerosis. 2001;155(1):149-156
PubMed | Link to Article

Chaaba R, Hammami S, Attia N, et al. Association of plasma cholesteryl ester transfer protein activity and polymorphism with coronary artery disease extent in Tunisian type II diabetic patients. Clin Biochem. 2005;38(4):373-378
PubMed | Link to Article

Chen J, Yokoyama T, Saito K, et al. Association of human cholesteryl ester transfer protein-TaqI polymorphisms with serum HDL cholesterol levels in a normolipemic Japanese rural population. J Epidemiol. 2002;12(2):77-84
PubMed | Link to Article

Choi HS, Park JB, Han KO, et al. A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women. Korean J Intern Med. 2002;17(2):83-87
PubMed

Corella D, Saiz C, Guillen M, et al. Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population. Atherosclerosis. 2000;152(2):367-376
PubMed | Link to Article

Ruiz-Narváez EA, Yang Y, Nakanishi Y, Kirchdorfer J, Campos H. APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica. J Lipid Res. 2005;46(12):2605-2613
PubMed | Link to Article

Cuchel M, Wolfe ML, deLemos AS, Rader DJ. The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower in African Americans than in Caucasians. Atherosclerosis. 2002;163(1):169-174
PubMed | Link to Article

McCaskie PA, Beilby JP, Chapman CM, et al. Cholesteryl ester transfer protein gene haplotypes, plasma high-density lipoprotein levels and the risk of coronary heart disease. Hum Genet. 2007;121(3-4):401-411
PubMed | Link to Article

Gudnason V, Kakko S, Nicaud V, et al. Cholesteryl ester transfer protein gene effect on CETP activity and plasma high-density lipoprotein in European populations: the EARS Group. Eur J Clin Invest. 1999;29(2):116-128
PubMed | Link to Article

Le Goff W, Guerin M, Nicaud V, et al. A novel cholesteryl ester transfer protein promoter polymorphism (-971G/A) associated with plasma high-density lipoprotein cholesterol levels: interaction with the TaqIB and -629C/A polymorphisms. Atherosclerosis. 2002;161(2):269-279
PubMed | Link to Article

Corbex M, Poirier O, Fumeron F, et al. Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction. Genet Epidemiol. 2000;19(1):64-80
PubMed | Link to Article

Dachet C, Poirier O, Cambien F, Chapman J, Rouis M. New functional promoter polymorphism, CETP/-629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels: role of Sp1/Sp3 in transcriptional regulation. Arterioscler Thromb Vasc Biol. 2000;20(2):507-515
PubMed | Link to Article

Fumeron F, Betoulle D, Luc G, et al. Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction. J Clin Invest. 1995;96(3):1664-1671
PubMed | Link to Article

Elosua R, Cupples LA, Fox CS, et al. Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: the Framingham Heart Study. Atherosclerosis. 2006;189(1):222-228
PubMed | Link to Article

Ordovas JM, Cupples LA, Corella D, et al. Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler Thromb Vasc Biol. 2000;20(5):1323-1329
PubMed | Link to Article

Freeman DJ, Griffin BA, Holmes AP, et al. Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors: associations between the TaqI B RFLP in the CETP gene and smoking and obesity. Arterioscler Thromb. 1994;14(3):336-344
PubMed | Link to Article

Friedlander Y, Leitersdorf E, Vecsler R, Funke H, Kark J. The contribution of candidate genes to the response of plasma lipids and lipoproteins to dietary challenge. Atherosclerosis. 2000;152(1):239-248
PubMed | Link to Article

Goto A, Sasai K, Suzuki S, et al. Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography. Atherosclerosis. 2001;159(1):153-163
PubMed | Link to Article

Gudnason V, Thormar K, Humphries SE. Interaction of the cholesteryl ester transfer protein I405V polymorphism with alcohol consumption in smoking and non-smoking healthy men, and the effect on plasma HDL cholesterol and apoAI concentration. Clin Genet. 1997;51(1):15-21
PubMed | Link to Article

Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr. 2006;83(3):592-600
PubMed

Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr. 2005;82(6):1260-1268
PubMed

Hannuksela ML, Liinamaa MJ, Kesaniemi YA, Savolainen MJ. Relation of polymorphisms in the cholesteryl ester transfer protein gene to transfer protein activity and plasma lipoprotein levels in alcohol drinkers. Atherosclerosis. 1994;110(1):35-44
PubMed | Link to Article

Lu H, Inazu A, Moriyama Y, et al. Haplotype analyses of cholesteryl ester transfer protein gene promoter: a clue to an unsolved mystery of TaqIB polymorphism. J Mol Med. 2003;81(4):246-255
PubMed

Hong SH, Kim YR, Song J, Kim JQ. Genetic variations of cholesterol ester transfer protein gene in Koreans. Hum Biol. 2001;73(6):815-821
PubMed | Link to Article

Bruce C, Sharp DS, Tall AR. Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia. J Lipid Res. 1998;39(5):1071-1078
PubMed

Curb JD, Abbott RD, Rodriguez BL, et al. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res. 2004;45(5):948-953
PubMed | Link to Article

Zhong S, Sharp DS, Grove JS, et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest. 1996;97(12):2917-2923
PubMed | Link to Article

Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004;351(25):2599-2610
PubMed | Link to Article

Hsu LA, Ko YL, Hsu KH, Ko YH, Lee YS. Genetic variations in the cholesteryl ester transfer protein gene and high density lipoprotein cholesterol levels in Taiwanese Chinese. Hum Genet. 2002;110(1):57-63
PubMed | Link to Article

Huang G-Y, Lu F-E, Li M-Z, et al. A comparative study on the allele frequencies of genetic variant Ile405Val of cholesteryl ester transfer protein and its influence on serum lipids in European and Asian populations. China J Modern Med. 1999;9(9):9-12

Hui SP. Frequency and effect on plasma lipoprotein metabolism of a mutation in the cholesteryl ester transfer protein gene in the Chinese [in Japanese]. Hokkaido Igaku Zasshi. 1997;72(3):319-327
PubMed

Horne BD, Camp NJ, Anderson JL, et al. Multiple less common genetic variants explain the association of the cholesteryl ester transfer protein gene with coronary artery disease. J Am Coll Cardiol. 2007;49(20):2053-2060
PubMed | Link to Article

Horne BD, Carlquist JF, Cannon-Albright LA, et al. High-resolution characterization of linkage disequilibrium structure and selection of tagging single nucleotide polymorphisms: application to the cholesteryl ester transfer protein gene. Ann Hum Genet. 2006;70(pt 4):524-534
PubMed | Link to Article

Whiting BM, Anderson JL, Muhlestein JB, et al. Candidate gene susceptibility variants predict intermediate end points but not angiographic coronary artery disease. Am Heart J. 2005;150(2):243-250
PubMed | Link to Article

Ikewaki K, Mabuchi H, Teramoto T, et al. Association of cholesteryl ester transfer protein activity and TaqIB polymorphism with lipoprotein variations in Japanese subjects. Metabolism. 2003;52(12):1564-1570
PubMed | Link to Article

Inazu A, Nishimura Y, Terada Y, Mabuchi H. Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population. J Hum Genet. 2001;46(4):172-177
PubMed | Link to Article

Keavney B, Palmer A, Parish S, et al. Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk. Int J Epidemiol. 2004;33(5):1002-1013
PubMed | Link to Article

Juvonen T, Savolainen MJ, Kairaluoma MI, et al. Polymorphisms at the apoB, apoA-I, and cholesteryl ester transfer protein gene loci in patients with gallbladder disease. J Lipid Res. 1995;36(4):804-812
PubMed

Kaplan DB, Schreiber R, Oliveira HC, et al. Cholesteryl ester transfer protein gene mutations in Brazilian hyperalphalipoproteinemia. Clin Genet. 2006;69(5):455-457
PubMed | Link to Article

Kark JD, Sinnreich R, Leitersdorf E, et al. Taq1B CETP polymorphism, plasma CETP, lipoproteins, apolipoproteins and sex differences in a Jewish population sample characterized by low HDL-cholesterol. Atherosclerosis. 2000;151(2):509-518
PubMed | Link to Article

Zheng KQ, Zhang SZ, He Y, et al. Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease. Chin Med J (Engl). 2004;117(9):1288-1292
PubMed

Kondo I, Berg K, Drayna D, Lawn R. DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels. Clin Genet. 1989;35(1):49-56
PubMed | Link to Article

Kuivenhoven JA, De KP, Boer JM, et al. Heterogeneity at the CETP gene locus: influence on plasma CETP concentrations and HDL cholesterol levels. Arterioscler Thromb Vasc Biol. 1997;17(3):560-568
PubMed | Link to Article

Liu J, Zhao D, Liu S, et al. Study on the distribution and association of cholesteryl ester transfer protein-TaqIB polymorphism and plasma concentration in general population [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2003;24(4):300-303
PubMed

Lu F-E, Huang G-Y, Wiebusch H, Funke H, Assmann G. Allele frequencies of mutations 373 Ala -> Pro and 451 Arg -> Gln in cholesterol ester transfer protein gene and their influences on lipid metabolism. Chin J Arterioscler. 1999;7(3):208-211

Mendis S, Shepherd J, Packard CJ, Gaffney D. Genetic variation in the cholesteryl ester transfer protein and apolipoprotein A-I genes and its relation to coronary heart disease in a Sri Lankan population. Atherosclerosis. 1990;83(1):21-27
PubMed | Link to Article

100

Miltiadous G, Hatzivassiliou M, Liberopoulos E, et al. Gene polymorphisms affecting HDL-cholesterol levels in the normolipidemic population. Nutr Metab Cardiovasc Dis. 2005;15(3):219-224
PubMed | Link to Article

101

Mitchell RJ, Earl L, Williams J, Bisucci T, Gasiamis H. Polymorphisms of the gene coding for the cholesteryl ester transfer protein and plasma lipid levels in Italian and Greek migrants to Australia. Hum Biol. 1994;66(1):13-25
PubMed

102

Motohashi Y, Maruyama T, Murata M, et al. Role of genetic factors (CETP gene Taq I B polymorphism and Apo A-I gene Msp I polymorphism) in serum HDL-C levels in women. Nutr Metab Cardiovasc Dis. 2004;14(1):6-14
PubMed | Link to Article

103

Mukherjee M, Shetty KR. Variations in high-density lipoprotein cholesterol in relation to physical activity and Taq 1B polymorphism of the cholesteryl ester transfer protein gene. Clin Genet. 2004;65(5):412-418
PubMed | Link to Article

104

Noone E, Roche HM, Black I, Tully AM, Gibney MJ. Effect of postprandial lipaemia and Taq 1B polymorphism of the cholesteryl ester transfer protein (CETP) gene on CETP mass, activity, associated lipoproteins and plasma lipids. Br J Nutr. 2000;84(2):203-209
PubMed

105

Talmud PJ, Hawe E, Robertson K, et al. Genetic and environmental determinants of plasma high density lipoprotein cholesterol and apolipoprotein AI concentrations in healthy middle-aged men. Ann Hum Genet. 2002;66(pt 2):111-124
PubMed | Link to Article

106

Okumura K, Matsui H, Kamiya H, et al. Differential effect of two common polymorphisms in the cholesteryl ester transfer protein gene on low-density lipoprotein particle size. Atherosclerosis. 2002;161(2):425-431
PubMed | Link to Article

107

Kakko S, Tamminen M, Paivansalo M, et al. Variation at the cholesteryl ester transfer protein gene in relation to plasma high density lipoproteins cholesterol levels and carotid intima-media thickness. Eur J Clin Invest. 2001;31(7):593-602
PubMed | Link to Article

108

Kakko S, Tamminen M, Paivansalo M, et al. Cholesteryl ester transfer protein gene polymorphisms are associated with carotid atherosclerosis in men. Eur J Clin Invest. 2000;30(1):18-25
PubMed | Link to Article

109

Kakko S, Tamminen M, Kesaniemi YA, Savolainen MJ. R451Q mutation in the cholesteryl ester transfer protein (CETP) gene is associated with high plasma CETP activity. Atherosclerosis. 1998;136(2):233-240
PubMed | Link to Article

110

Tamminen M, Kakko S, Kesaniemi YA, Savolainen MJ. A polymorphic site in the 3′ untranslated region of the cholesteryl ester transfer protein (CETP) gene is associated with low CETP activity. Atherosclerosis. 1996;124(2):237-247
PubMed | Link to Article

111

Kauma H, Savolainen MJ, Heikkila R, et al. Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors. Hum Genet. 1996;97(2):156-162
PubMed | Link to Article

112

Padmaja N, Ravindra KM, Soya SS, Adithan C. Common variants of cholesteryl ester transfer protein gene and their association with lipid parameters in healthy volunteers of Tamilian population. Clin Chim Acta. 2007;375(1-2):140-146
PubMed | Link to Article

113

Zee RY, Cook NR, Cheng S, et al. Multi-locus candidate gene polymorphisms and risk of myocardial infarction: a population-based, prospective genetic analysis. J Thromb Haemost. 2006;4(2):341-348
PubMed | Link to Article

114

Liu S, Schmitz C, Stampfer MJ, et al. A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men [published correction appears in Atherosclerosis. 2003;166(2):415]. Atherosclerosis. 2002;161(2):469-474
PubMed | Link to Article

115

Zee RY, Cook NR, Cheng S, et al. Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet. 2004;13(4):389-396
PubMed | Link to Article

116

Plat J, Mensink RP. Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption. Eur J Clin Invest. 2002;32(4):242-250
PubMed | Link to Article

117

Borggreve SE, Hillege HL, Wolffenbuttel BH, et al. An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: a population-based study. J Clin Endocrinol Metab. 2006;91(9):3382-3388
PubMed | Link to Article

118

Asselbergs FW, Moore JH, van den Berg MP, et al. A role for CETP TaqIB polymorphism in determining susceptibility to atrial fibrillation: a nested case control study. BMC Med Genet. 2006;739
PubMed | Link to Article

119

Borggreve SE, Hillege HL, Wolffenbuttel BH, et al. The effect of cholesteryl ester transfer protein -629C->A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides. J Clin Endocrinol Metab. 2005;90(7):4198-4204
PubMed | Link to Article

120

Dullaart RP, Borggreve SE, Hillege HL, Dallinga-Thie GM. The association of HDL cholesterol concentration with the -629C>A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer. Scand J Clin Lab Invest. 2008;68(2):99-105
PubMed | Link to Article

121

van Himbergen TM, van der Schouw YT, Voorbij HA, et al. Paraoxonase (PON1) and the risk for coronary heart disease and myocardial infarction in a general population of Dutch women [published ahead of print December 26, 2007]. Atherosclerosis2007
PubMed

122

Qin Q, Zhao B-R, Geng J, et al. The association of the lipoprotein lipase S447X and cholesteryl ester transfer protein TaqIB polymorphism with coronary heart disease. Chin J Cardiol. 2004;32(6):522-525

123

Eiriksdottir G, Bolla MK, Thorsson B, et al. The -629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men. Atherosclerosis. 2001;159(1):187-192
PubMed | Link to Article

124

Riemens SC, van Tol A, Stulp BK, Dullaart RP. Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men. J Lipid Res. 1999;40(8):1467-1474
PubMed

125

Sandhofer A, Tatarczyk T, Laimer M, et al. The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome [published ahead of print January 24, 2008]. Obesity (Silver Spring). 2008;16(4):919-922
PubMed | Link to Article

126

Weitgasser R, Galvan G, Malaimare L, et al. Cholesteryl ester transfer protein TaqIB polymorphism and its relation to parameters of the insulin resistance syndrome in an Austrian cohort. Biomed Pharmacother. 2004;58(10):619-627
PubMed | Link to Article

127

Arai H, Yamamoto A, Matsuzawa Y, et al. Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000. J Atheroscler Thromb. 2005;12(5):240-250
PubMed | Link to Article

128

Tai ES, Ordovas JM, Corella D, et al. The TaqIB and -629C>A polymorphisms at the cholesteryl ester transfer protein locus: associations with lipid levels in a multiethnic population: the 1998 Singapore National Health Survey. Clin Genet. 2003;63(1):19-30
PubMed | Link to Article

129

Song GJ, Han GH, Chae JJ, et al. The effects of the cholesterol ester transfer protein gene and environmental factors on the plasma high density lipoprotein cholesterol levels in the Korean population. Mol Cells. 1997;7(5):615-619
PubMed

130

Sorlí JV, Corella D, Francés F, et al. The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population. Clin Chim Acta. 2006;366(1-2):196-203
PubMed | Link to Article

131

Deguchi H, Pecheniuk NM, Elias DJ, Averell PM, Griffin JH. High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men. Circulation. 2005;112(6):893-899
PubMed | Link to Article

132

Pecheniuk NM, Deguchi H, Elias DJ, Xu X, Griffin JH. Cholesteryl ester transfer protein genotypes associated with venous thrombosis and dyslipoproteinemia in males. J Thromb Haemost. 2006;4(9):2080-2082
PubMed | Link to Article

133

Tenkanen H, Koshinen P, Kontula K, et al. Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease. Hum Genet. 1991;87(5):574-578
PubMed | Link to Article

134

Thompson JF, Lira ME, Durham LK, et al. Polymorphisms in the CETP gene and association with CETP mass and HDL levels. Atherosclerosis. 2003;167(2):195-204
PubMed | Link to Article

135

Tobin MD, Braund PS, Burton PR, et al. Genotypes and haplotypes predisposing to myocardial infarction: a multilocus case-control study. Eur Heart J. 2004;25(6):459-467
PubMed | Link to Article

136

Tsujita Y, Nakamura Y, Zhang Q, et al. The association between high-density lipoprotein cholesterol level and cholesteryl ester transfer protein TaqIB gene polymorphism is influenced by alcohol drinking in a population-based sample. Atherosclerosis. 2007;191(1):199-205
PubMed | Link to Article

137

Hodoğlugil U, Williamson DW, Huang Y, Mahley RW. An interaction between the TaqIB polymorphism of cholesterol ester transfer protein and smoking is associated with changes in plasma high-density lipoprotein cholesterol levels in Turks. Clin Genet. 2005;68(2):118-127
PubMed | Link to Article

138

Vergani C, Lucchi T, Caloni M, et al. I405V polymorphism of the cholesteryl ester transfer protein (CETP) gene in young and very old people. Arch Gerontol Geriatr. 2006;43(2):213-221
PubMed | Link to Article

139

Lucchi T, Arosio B, Caloni M, et al. I405V polymorphism of the cholesteryl ester transfer protein gene in young and very old individuals [in Italian]. Ann Ital Med Int. 2005;20(1):45-50
PubMed

140

Martinelli N, Trabetti E, Bassi A, et al. The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study. Atherosclerosis. 2007;191(2):409-417
PubMed | Link to Article

141

Vohl MC, Lamarche B, Pascot A, et al. Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome. Int J Obes Relat Metab Disord. 1999;23(9):918-925
PubMed | Link to Article

142

Wang W, Zhou X, Liu F, Hu H-N, Han D-F. Association of the TaqIB polymorphism and D442G mutation of cholesteryl ester transfer protein gene with coronary heart disease. Chin J Cardiol. 2004;32(11):981-985

143

Freeman DJ, Samani NJ, Wilson V, et al. A polymorphism of the cholesteryl ester transfer protein gene predicts cardiovascular events in non-smokers in the West of Scotland Coronary Prevention Study. Eur Heart J. 2003;24(20):1833-1842
PubMed | Link to Article

144

Wu Y, Bai H, Liu R, Liu Y, Liu BW. Analysis of cholesterol ester transfer protein gene Taq IB and -629 C/A polymorphisms in patients with endogenous hypertriglyceridemia in Chinese population [in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23(6):640-646
PubMed

145

Yilmaz H, Isbir T, Agachan B, Karaali ZE. Effects of cholesterol ester transfer protein Taq1B gene polymorphism on serum lipoprotein levels in Turkish coronary artery disease patients. Cell Biochem Funct. 2005;23(1):23-28
PubMed | Link to Article

146

Yilmaz H, Agachan B, Karaali ZE, Isbir T. Taq1B polymorphism of CETP gene on lipid abnormalities in patients with type II diabetes mellitus. Int J Mol Med. 2004;13(6):889-893
PubMed

147

Isbir T, Yilmaz H, Agachan B, Karaali ZE. Cholesterol ester transfer protein, apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population. Clin Genet. 2003;64(3):228-234
PubMed | Link to Article

148

Jang Y, Kim JY, Kim OY, et al. The -1131T→C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men. Am J Clin Nutr. 2004;80(4):832-840
PubMed

149

Dedoussis GV, Panagiotakos DB, Louizou E, et al. Cholesteryl ester-transfer protein (CETP) polymorphism and the association of acute coronary syndromes by obesity status in Greek subjects: the CARDIO2000-GENE study. Hum Hered. 2007;63(3-4):155-161
PubMed | Link to Article

150

Falchi A, Piras IS, Vona G, et al. Cholesteryl ester transfer protein gene polymorphisms are associated with coronary artery disease in Corsican population (France). Exp Mol Pathol. 2007;83(1):25-29
PubMed | Link to Article

151

Falchi A, Giovannoni L, Piras IS, et al. Prevalence of genetic risk factors for coronary artery disease in Corsica island (France). Exp Mol Pathol. 2005;79(3):210-213
PubMed | Link to Article

152

Andrikopoulos GK, Richter DJ, Needham EW, et al. Association of the ile405val mutation in cholesteryl ester transfer protein gene with risk of acute myocardial infarction. Heart. 2004;90(11):1336-1337
PubMed | Link to Article

153

Morgan TM, Krumholz HM, Lifton RP, Spertus JA. Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA. 2007;297(14):1551-1561
PubMed | Link to Article

154

van Acker BA, Botma GJ, Zwinderman AH, et al. High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants [published ahead of print December 26, 2007]. AtherosclerosisLink to Article
PubMed

155

Isaacs A, Sayed-Tabatabaei FA, Hofman A, et al. The cholesteryl ester transfer protein I405V polymorphism is associated with increased high-density lipoprotein levels and decreased risk of myocardial infarction: the Rotterdam Study. Eur J Cardiovasc Prev Rehabil. 2007;14(3):419-421
PubMed | Link to Article

156

Isaacs A, Aulchenko YS, Hofman A, et al. Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on serum high-density lipoprotein cholesterol levels. J Clin Endocrinol Metab. 2007;92(7):2680-2687
PubMed | Link to Article

157

Silva MC, Janssens AC, Hofman A, Witteman JC, Duijn CM. Cholesteryl ester transfer protein gene and coronary heart disease mortality: the Rotterdam Study. J Am Geriatr Soc. 2007;55(9):1483-1484
PubMed | Link to Article

158

Wu JH, Lee YT, Hsu HC, Hsieh LL. Influence of CETP gene variation on plasma lipid levels and coronary heart disease: a survey in Taiwan. Atherosclerosis. 2001;159(2):451-458
PubMed | Link to Article

159

Yamada Y, Izawa H, Ichihara S, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002;347(24):1916-1923
PubMed | Link to Article

160

Yan S-K, Zhu Y-L, Cheng S, et al. Relationship between coronary heart disease and Taq IB & Msp I polymorphisms of cholesteryl ester transfer protein gene in Han nationality. Chin J Lab Med. 2004;27(10):671-675

161

Zhang G-B, Jiang Z-W, Sun B-G, et al. Relationship of Taq IB polymorphism in the cholesteryl ester transfer protein gene to coronary artery disease. Chin J Arterioscler. 2005;13(1):88-90

162

Zhao S-P, Li H, Xiao Z-J, Nie S. The effect of cholesteryl ester transfer protein TaqIB gene polymorphism on lipoprotein level. Chin J Cardiol. 2004;32816-818

163

Zheng K, Zhang S, Zhang L, et al. Carriers of three polymorphisms of cholesteryl ester transfer protein gene are at increased risk to coronary heart disease in a Chinese population. Int J Cardiol. 2005;103(3):259-265
PubMed | Link to Article

164

Zheng KQ, Zhang SZ, Zhang L, et al. A novel missense mutation (L296 Q) in cholesteryl ester transfer protein gene related to coronary heart disease. Acta Biochim Biophys Sin (Shanghai). 2004;36(1):33-36
PubMed | Link to Article

165

Zheng KQ, Zhang SZ, Zhang KL, et al. Study on the association of cholesteryl ester transfer protein gene mutations with the susceptibility to coronary atherosclerotic heart disease [in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003;20(1):23-26
PubMed

166

Pharmacogenetics and risk of cardiovascular disease (PARC) resequencing project. http://droog.gs.washington.edu/parc/. Accessed January 23, 2008

167

Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancet. 2003;361(9357):598-604
PubMed | Link to Article

168

Keavney B, Danesh J, Parish S, et al. Fibrinogen and coronary heart disease: test of causality by ‘Mendelian randomization.’ Int J Epidemiol. 2006;35(4):935-943
PubMed | Link to Article

169

Davey Smith G, Ebrahim S. What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ. 2005;330(7499):1076-1079
PubMed | Link to Article

170

Boekholdt SM, Thompson JF. Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease. J Lipid Res. 2003;44(6):1080-1093
PubMed | Link to Article

171

Krishna R, Anderson MS, Bergman AJ, et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet. 2007;370(9603):1907-1914
PubMed | Link to Article

Figures

Place holder to copy figure label and caption

Figure 1. Study Flow Diagram

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

Place holder to copy figure label and caption

Figure 2. Associations of CETP Genotypes With CETP Phenotypes and Lipid Levels

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

Place holder to copy figure label and caption

Figure 3. Mean Differences in HDL-C Levels Associated With CETP Genotypes, Grouped by Recorded Study Characteristics

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

Place holder to copy figure label and caption

Figure 4. CETP Genotypes and Coronary Risk, Grouped by Recorded Study Characteristics

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

Place holder to copy figure label and caption

Figure 5. Observed Per-Allele Odds Ratios for Coronary Disease With CETP Variants vs Odds Ratios Derived From Available Prospective Studies of HDL-C Levels

Grahic Jump Location

View Large | Save Figure | Download Slide (.ppt) | View in Article Context

Tables

Table 1. Description of CETP Genotypes Included in the Review

View Large | Save Table | Download Slide (.ppt) | View in Article Context

Table 2. Summary of Data Available on CETP Genotypes, CETP Phenotypes, Lipid Levels, and Coronary Outcomes^a

View Large | Save Table | Download Slide (.ppt) | View in Article Context

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal