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No Structural Mutation in the Dopamine D2 Receptor Gene in Alcoholism or Schizophrenia Analysis Using Denaturing Gradient Gel Electrophoresis

Pablo V. Gejman, MD; Anca Ram, MD; Joel Gelernter, MD; Eitan Friedman, MD; Qiuhe Cao, MD; David Pickar, MD; Kenneth Blum, PhD; Ernest P. Noble, MD, PhD; Henry R. Kranzler, MD; Stephanie O'Malley, PhD; Dean H. Hamer, MD; Flanagan Whitsitt, MA; Peter Rao, MD; Lynn E. DeLisi, MD; Matti Virkkunen, MD; Markku Linnoila, MD, PhD; David Goldman, MD; Elliot S. Gershon, MD
JAMA. 1994;271(3):204-208. doi:10.1001/jama.1994.03510270050038.
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Objective.  —To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene.

Design.  —Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants.

Setting.  —Patients and controls from clinical and epidemiologic collections in the United States and Europe.

Patients.  —A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taq site 3' to the DRD2gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white.

Main Outcome Measures.  —Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups.

Results.  —We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia.

Conclusion.  —No structural coding abnormalities in the DRD2gene are present in alcoholism or schizophrenia.(JAMA. 1994;271:204-208)


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