Alcohology Research Laboratory, Medical School, University of Crete, 71500, Heraklion, Crete, Greece.
Department of Gastroenterology, University Hospital Heraklion, 71500, Heraklion, Crete, Greece.
Psychopharmacology (Berl). 2018 Jun;235(6):1845-1865. doi: 10.1007/s00213-018-4918-4. Epub 2018 May 2.
Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by environmental causal heterogeneity. Risk factors associated with its etiology have a genetic component. GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter in mammalian brain. GABA receptors are believed to mediate some of the physiological and behavioral actions of alcohol. In this critical review, relevant genetic terms and type and methodology of the genetic studies are briefly explained. Postulated candidate genes that encode subunits of GABA receptors, with all the reported SNPs, are presented. Genetic studies and meta-analyses examining polymorphisms of the GABA receptor and their association with AUD predisposition are presented. The data are critically examined with reference to recent GWAS studies that failed to show relations between GABA receptors and AUD. Restrictions and perspectives of the different findings are discussed.
酒精使用障碍（AUD）是一种在全球范围内具有高患病率和严重公共卫生影响的慢性、复发性神经精神疾病。它具有复杂性和多基因性，遗传率约为 50%，并受到环境因果异质性的影响。与病因相关的风险因素具有遗传成分。GABA（γ-氨基丁酸）是哺乳动物大脑中的主要抑制性神经递质。GABA 受体被认为介导了酒精的一些生理和行为作用。在这篇重要的综述中，简要解释了相关的遗传术语和遗传研究的类型和方法。提出了编码 GABA 受体亚基的假定候选基因，并列出了所有报告的 SNP。介绍了研究 GABA 受体多态性及其与 AUD 易感性关联的遗传研究和荟萃分析。参考最近的 GWAS 研究，这些研究未能显示 GABA 受体与 AUD 之间的关系，对数据进行了批判性检查。讨论了不同发现的局限性和观点。
