Dick Danielle M, Edenberg Howard J, Xuei Xiaoling, Goate Alison, Hesselbrock Victor, Schuckit Marc, Crowe Raymond, Foroud Tatiana
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., Indianapolis, IN 46202-525, USA.
Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):24-8. doi: 10.1002/ajmg.b.30058.
A substantial body of literature suggests that gamma-aminobutyric acid (GABA) may be involved in the neurochemical pathways contributing to alcohol use and related disorders. Chromosome 5 contains a cluster of GABA(A) receptor genes, GABRA1, GABRA6, GABRB2, and GABRG2, which have been among the most extensively studied in relation to alcohol use. These studies have yielded mixed results. Using data from large, multiplex alcoholic families collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA), we sought to provide more conclusive evidence regarding the role of the GABA(A) receptor genes on chromosome 5. Multiple single nucleotide polymorphisms (SNPs) were tested in each of the four chromosome 5q GABA(A) receptor genes, and we conducted both classic trio-based association analyzes and extended pedigree analyzes. We found no consistent evidence of association with alcohol dependence or alcohol dependence comorbid with antisocial personality disorder (ASPD) for any of the regions tested in the chromosome 5 GABA(A) receptor genes. These analyses suggest that the GABA(A) receptor genes on chromosome 5 do not play a strong role in alcohol dependence. Future studies are planned to test whether these genes are more important in influencing behavioral endophenotypes related to the risk of alcohol dependence.
大量文献表明，γ-氨基丁酸（GABA）可能参与了导致酒精使用及相关障碍的神经化学途径。5号染色体包含一组GABA(A)受体基因，即GABRA1、GABRA6、GABRB2和GABRG2，这些基因是与酒精使用相关研究最为广泛的基因之一。这些研究结果不一。利用作为酒精中毒遗传学合作研究（COGA）一部分收集的大型多重酒精中毒家族的数据，我们试图提供更确凿的证据，证明5号染色体上GABA(A)受体基因的作用。对5号染色体上四个GABA(A)受体基因中的每一个都测试了多个单核苷酸多态性（SNP），并且我们进行了经典的基于三联体的关联分析和扩展家系分析。我们没有发现5号染色体GABA(A)受体基因中测试的任何区域与酒精依赖或与反社会人格障碍（ASPD）共病的酒精依赖存在一致的关联证据。这些分析表明，5号染色体上的GABA(A)受体基因在酒精依赖中不发挥重要作用。计划未来的研究来测试这些基因在影响与酒精依赖风险相关的行为内表型方面是否更重要。
