Parsian A, Cloninger C R
Departments of Psychiatry and Genetics, Washington University School of Medicine, St. Louis, Missouri.
Alcohol Clin Exp Res. 1997 May;21(3):430-433. doi: 10.1111/j.1530-0277.1997.tb03787.x.
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA effects are largely mediated by binding to the postsynaptic GABA receptor, causing the opening of an integral chloride-ion channel. The GABA antagonists picrotoxin and bicuculline reduce some ethanol-induced behaviors, such as motor impairment, sedation, and hypnosis. The role of this receptor in alcoholism is further supported by effective alleviation of alcohol withdrawal symptoms by GABA agonists. To determine the role of the GABA, receptor (GABR) genes in the development of alcoholism, we have used α and α simple sequence repeat polymorphisms in a sample of unrelated alcoholics, alcoholic probands with both parents, and psychiatrically normal controls. For the GABRα gene, the differences between allele frequencies, when all alleles were compared together, were not significant between total alcoholics, subtypes of alcoholics, and normal controls. However, for GABRα , the differences between total alcoholics and normal controls were significant when all alleles were compared together. The differences between subtypes of alcoholics and normal controls were not significant. The results of haplotype relative risk analysis for both genes, GABRα and GABRα , were also negative. It is possible that the sample size in the haplotype relative risk is too small to have power to detect the differences in transmitted versus nontransmitted alleles. There is a need for a replication study in a large family sample, that will allow haplotype relative risk or affected sib-pair analysis.
γ-氨基丁酸（GABA）是大脑中主要的抑制性神经递质。GABA的作用主要是通过与突触后GABA受体结合来介导的，从而导致整合氯离子通道的开放。GABA拮抗剂印防己毒素和荷包牡丹碱可减轻一些乙醇诱导的行为，如运动障碍、镇静和催眠。GABA激动剂能有效缓解酒精戒断症状，进一步支持了该受体在酒精中毒中的作用。为了确定GABA受体（GABR）基因在酒精中毒发展中的作用，我们在一组无关的酗酒者、父母均酗酒的酗酒先证者以及精神正常的对照组中使用了α和α简单序列重复多态性。对于GABRα基因，当将所有等位基因一起比较时，总酗酒者、酗酒者亚型与正常对照组之间的等位基因频率差异不显著。然而，对于GABRα，当将所有等位基因一起比较时，总酗酒者与正常对照组之间的差异是显著的。酗酒者亚型与正常对照组之间的差异不显著。对GABRα和GABRα这两个基因的单倍型相对风险分析结果也均为阴性。有可能单倍型相对风险分析中的样本量过小，以至于没有能力检测传递等位基因与未传递等位基因之间的差异。需要在一个大型家系样本中进行重复研究，以便进行单倍型相对风险分析或患病同胞对分析。
