Department of Molecular and Integrative Neurosciences, the Scripps Research Institute, La Jolla, CA, USA.
Am J Psychiatry. 2013 Feb;170(2):154-64. doi: 10.1176/appi.ajp.2012.12010113.
Although tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans. General population studies have demonstrated that substance dependence has a substantially heritable component (approximately 50% of the risk resulting from genetic influences); however, fewer studies have investigated the role of genetics in the risk for substance dependence in Native Americans.
The authors present a literature review of the evidence for a genetic component in the etiology of substance dependence in Native Americans, including studies of heritability, linkage analyses, and candidate genes.
Evidence for the heritability of alcohol and drug dependence was found. Linkage analyses revealed that genes influencing risk for substance dependence and related phenotypes, such as body mass index (BMI), drug tolerance, EEG patterns, and externalizing traits, reside on several chromosome regions identified in other population samples. Overlap in the gene locations for substance dependence and BMI suggests that a common genetic substrate may exist for disorders of consumption. Studies of the genes that code for alcohol-metabolizing enzymes have not revealed any risk variants specific to Native American populations, although most Native Americans lack protective variants seen in other populations. Other candidate genes associated with substance dependence phenotypes in Native Americans include OPRM1, CRN1, COMT, GABRA2, MAOA, and HTR3-B.
Substance dependence has a substantial genetic component in Native Americans, similar in magnitude to that reported for other populations. The high rates of substance dependence seen in some tribes is likely a combination of a lack of genetic protective factors (metabolizing enzyme variants) combined with genetically mediated risk factors (externalizing traits, consumption drive, and drug sensitivity or tolerance) that combine with key environmental factors (trauma exposure, early age at onset of use, and environmental hardship) to produce an elevated risk for the disorder.
尽管部落之间在使用酒精和药物方面存在差异，但药物依赖是美洲原住民面临的主要健康问题之一。一般人群研究表明，药物依赖具有很大的遗传成分（约 50%的风险来自遗传影响）；然而，很少有研究调查遗传在美洲原住民药物依赖风险中的作用。
作者对美洲原住民药物依赖病因学中遗传成分的证据进行了文献回顾，包括遗传力研究、连锁分析和候选基因研究。
发现了酒精和药物依赖遗传的证据。连锁分析显示，影响物质依赖和相关表型（如体重指数 (BMI)、药物耐受性、脑电图模式和外化特征）风险的基因位于其他人群样本中确定的几个染色体区域。物质依赖和 BMI 的基因位置重叠表明，消费障碍可能存在共同的遗传基础。编码酒精代谢酶的基因研究并未发现任何特定于美洲原住民人群的风险变异，尽管大多数美洲原住民缺乏其他人群中存在的保护变异。与美洲原住民物质依赖表型相关的其他候选基因包括 OPRM1、CRN1、COMT、GABRA2、MAOA 和 HTR3-B。
药物依赖在美洲原住民中有很大的遗传成分，与其他人群报告的程度相似。一些部落中看到的高物质依赖率很可能是缺乏遗传保护因素（代谢酶变异）与遗传介导的风险因素（外化特征、消费驱动力和药物敏感性或耐受性）相结合的结果，再加上关键的环境因素（创伤暴露、开始使用的年龄早和环境困难），导致该疾病的风险增加。
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