酒精中毒和阿片类药物成瘾易感性和治疗的遗传变异:药物基因组学方法

IF 0.7 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY AIMS Molecular Science Pub Date : 2021-01-01 DOI:10.3934/molsci.2021016
Catherine Demery-Poulos, Joseph M Chambers
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引用次数: 0

摘要

酒精和阿片类药物滥用从个人到社会层面都具有普遍和有害的后果。遗传对酒精中毒的影响程度已经研究了几十年,自从之前发现两种药物代动力学变异对酒精中毒有很强的保护作用以来,产生了推测性的和经常不一致的结果。成瘾的神经生物学涉及数不清的基因,这些基因具有组合和上位性的相互作用,因此很难得出具体的结论。相比之下,酒精中毒治疗中的药物基因组变异产生了更直接的临床效用,同时也强调了成瘾进展的关键途径。提高对酒精滥用遗传易感性的理解对阿片类药物成瘾和治疗具有内在意义,因为这两种药物诱导相同的奖励途径。这篇综述概述了目前关于酒精中毒遗传易感性的知识、治疗方法和研究,重点是多巴胺能系统内的药效学变化以及对阿片类药物滥用的共同影响。随着新的研究扩大了成瘾对大脑、身体和后代的影响范围,成瘾的表型似乎变得更加复杂,多面性和高度多基因性。
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Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach
Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.
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来源期刊
AIMS Molecular Science
AIMS Molecular Science BIOCHEMISTRY & MOLECULAR BIOLOGY-
自引率
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发文量
4
审稿时长
5 weeks
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