Town T, Abdullah L, Crawford F, Schinka J, Ordorica P I, Francis E, Hughes P, Duara R, Mullan M
The Roskamp Institute, University of South Florida, Tampa, Florida 33613, USA.
Am J Med Genet. 1999 Oct 15;88(5):458-61.
Genetic association studies have implicated the TaqI A1 allele of the human dopamine D2 receptor gene (DRD2) as a risk-determining factor for alcohol dependency. However, as alcoholism is a disease of polygenic inheritance, the percentage of overall disease variance explained by the TaqI A1 allele is small. In searching for other genetic loci that may, either alone or in combination with DRD2, enhance prediction of alcoholism, we have found a novel association between a functional coding variant (+118A) within the human mu-opioid receptor gene and alcohol dependency. However, no association was detected between the DRD2 TaqI A1 allele and alcoholism in our sample nor did we find synergy between +118A and TaqI A1 alleles on prediction of risk for the disease. These results suggest that, at the molecular level, the endogenous mu-opioid receptor system is a contributing factor to the etiology of alcoholism.
基因关联研究表明，人类多巴胺D2受体基因（DRD2）的TaqI A1等位基因是酒精依赖的风险决定因素。然而，由于酒精中毒是一种多基因遗传疾病，TaqI A1等位基因所解释的总体疾病变异百分比很小。在寻找可能单独或与DRD2结合增强酒精中毒预测的其他基因位点时，我们发现人类μ-阿片受体基因内的一个功能性编码变体（+118A）与酒精依赖之间存在新的关联。然而，在我们的样本中未检测到DRD2 TaqI A1等位基因与酒精中毒之间的关联，我们也未发现+118A和TaqI A1等位基因在疾病风险预测上存在协同作用。这些结果表明，在内分子水平上，内源性μ-阿片受体系统是酒精中毒病因的一个促成因素。
