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[成瘾的遗传学视角]

[A genetic view of addiction].

作者信息

Ramoz Nicolas, Gorwood Philip

机构信息

Inserm unité 894, centre de psychiatrie et neurosciences, 2ter, rue d'Alésia, 75014 Paris, France.

Inserm unité 894, centre de psychiatrie et neurosciences, 2ter, rue d'Alésia, 75014 Paris, France - Clinique des maladies mentales et de l'encéphale (CMME), hôpital Sainte-Anne, université Paris Descartes, 100, rue de la santé, 75674 Paris Cedex 14, France.

出版信息

Med Sci (Paris). 2015 Apr;31(4):432-8. doi: 10.1051/medsci/20153104018. Epub 2015 May 8.

Abstract

The genetic analyses of addictions recently converted to genome-wide association studies (GWAS) and thanks to national and international consortia, allowed to recruit large cohorts of patients. This approach allowed the identification of the first susceptibility gene in addiction (tobacco), with genes CHRNA5, CHRNA3 and CHRNB4 encoding the α5, α3 and b4 subunits involved in the formation of nicotinic receptors, explaining 14% of the attributable risk for tobacco dependence. Variants of ADH1B and ADH1C genes encoding alcohol dehydrogenases enzymes have also been consistently associated, this time with alcohol dependence (AD). Finally, DRD2 and ANKK1 genes, involved in the dopaminergic pathway, and which were initially associated with AD, are now considered to be involved in a broader phenotype (addiction to psychoactive substances) including opiates. Future directions in molecular study of addiction are gene x environment interactions though the epigenetic approach. Numerous studies already investigated the methylome in addiction, including histone and microRNA modifications.

摘要

成瘾的遗传分析最近转向了全基因组关联研究(GWAS),并且由于国内和国际联盟,得以招募大量患者队列。这种方法使得能够识别出成瘾(烟草成瘾)中的首个易感基因,其中CHRNA5、CHRNA3和CHRNB4基因编码参与烟碱型受体形成的α5、α3和b4亚基,解释了14%的烟草依赖归因风险。编码酒精脱氢酶的ADH1B和ADH1C基因的变异也一直与之相关,这次是与酒精依赖(AD)相关。最后,参与多巴胺能途径且最初与AD相关的DRD2和ANKK1基因,现在被认为参与了包括阿片类药物在内的更广泛的表型(精神活性物质成瘾)。成瘾分子研究的未来方向是通过表观遗传学方法研究基因与环境的相互作用。许多研究已经对成瘾中的甲基化组进行了研究,包括组蛋白和微小RNA修饰。

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