MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, P. O. Box 80, London SE58AF, England.
Curr Psychiatry Rep. 2009 Oct;11(5):364-9. doi: 10.1007/s11920-009-0055-4.
Heritability estimates for alcoholism range from 50% to 60%, pointing out the importance of genetic and environmental factors in its etiology. This review highlights recent advances in translational work investigating genetic influences on alcoholism. We focus on genetic research involving corticotropin-releasing factor, glutamatergic, and opioidergic systems. Variation in the CRF1 receptor gene has been shown to moderate stress-induced alcohol drinking (gene-environment interaction) in animals, and this finding was recently extended to humans. Also, the hyperglutamatergic state, first observed during withdrawal from chronic alcohol exposure in animal models, is associated with aversive and dysphoric states in alcoholics. Pharmacogenetic studies of naltrexone efficacy are in the clinical stages, and recent studies confirmed a differential response dependent on the mu-opioid receptor genotype. Such advances will be essential for the effective treatment of alcoholism in the future.
遗传性酗酒的估计范围在 50%至 60%之间，指出了遗传和环境因素在其病因学中的重要性。本综述重点介绍了遗传影响酗酒的转化研究的最新进展。我们专注于涉及促肾上腺皮质素释放因子、谷氨酸能和阿片能系统的遗传研究。研究表明，CRF1 受体基因的变异可调节动物应激诱导的饮酒（基因-环境相互作用），这一发现最近扩展到人类。此外，在动物模型中慢性酒精暴露戒断期间首次观察到的过度谷氨酸能状态与酗酒者的不愉快和不适状态有关。纳曲酮疗效的遗传药理学研究处于临床阶段，最近的研究证实了对μ-阿片受体基因型的不同反应。这些进展对于未来酗酒的有效治疗至关重要。
