Helicobacter pylori Susceptibility in the GWAS Era

El-Omar EM. — Wed, 08 May 2013 00:00:00 GMT

Helicobacter pylori infection remains one of the most common chronic bacterial infections worldwide and is causally linked to the pathogenesis of peptic ulcer disease, gastric adenocarcinoma, and MALT (mucosa-associated lymphoid tissue) lymphoma. However, the majority of infected patients generally remain asymptomatic and never develop significant disease. Because of its wide prevalence and causal association with serious disease outcomes, this infection has deservedly commanded the attention and dedication of researchers across the globe.

Identification of Genetic Loci Associated With Helicobacter pylori Serologic Status GWAS of H pylori Infection Susceptibility

Mayerle J, den Hoed CM, Schurmann C, et al. — Wed, 08 May 2013 00:00:00 GMT

Importance

Helicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H pylori susceptibility.

Objective

To identify genetic loci associated with H pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling.

Design, Setting, and Participants

Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n = 3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n = 7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n = 991]), and fecal H pylori antigen in SHIP-TREND (n = 961).

Main Outcomes and Measures

H pylori seroprevalence.

Results

Of 10 938 participants, 6160 (56.3%) were seropositive for H pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P = 1.4 × 10⁻¹⁸; odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P = 2.1 × 10⁻⁸; odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (β = −0.23 [95% CI, −0.34 to −0.11]; P = 2.1 × 10⁻⁴). Individuals with high fecal H pylori antigen titers (optical density >1) also exhibited the highest 25% of TLR1 expression levels (P = .01 by χ² test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP.

Conclusions and Relevance

GWAS meta-analysis identified an association between TLR1 and H pylori seroprevalence, a finding that requires replication in nonwhite populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H pylori infection.

CDC Releases First National Guidelines on Managing Q Fever

Wed, 08 May 2013 00:00:00 GMT

Clinicians now have guidelines to help them diagnose and treat Q fever, a worldwide zoonotic disease caused by the Coxiella burnetii bacterium. The new guidelines, the first to be released in the United States, have been in development for 3 years.

JAMA: Bacterial Infections Topic Collection

Helicobacter pylori Susceptibility in the GWAS Era

Identification of Genetic Loci Associated With Helicobacter pylori Serologic Status GWAS of H pylori Infection Susceptibility

CDC Releases First National Guidelines on Managing Q Fever