National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi, India.
BMC Med Genet. 2010 Feb 11;11:24. doi: 10.1186/1471-2350-11-24.
Dopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three single nucleotide polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian subjects.
In a retrospective analysis, genetic association of three polymorphisms from DRD2 gene with alcohol dependence was investigated using a case-control approach. Alcohol dependence was determined by DSM-IV criteria and a total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were recruited. Odds ratio and confidence interval was calculated to determine risk conferred by a predisposing allele/genotype/haplotype. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair-wise interactions between SNPs.
The study showed a significant association of -141C Ins allele and a trend of association of TaqI A1 allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins and TaqI A1 alleles (-141C Ins-A-A1) seems to confer approximately 2.5 times more risk to develop alcohol dependence.
The study provides preliminary insight into genetic risk to alcohol dependence in Indian males. Two polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical implications among Indian alcoholic subjects.
多巴胺是一种重要的神经递质，参与大脑中的奖励机制，从而影响酒精依赖的发展和复发。在第 11 号染色体（q22-q23）上的多巴胺 D2 受体（DRD2）基因已被发现与通过涉及酒精患者激励显著归因和渴望的机制与增加的酒精消费相关。因此，我们调查了 DRD2 基因中的三个单核苷酸多态性（SNP）与北印度受试者中酒精依赖的关联。
在回顾性分析中，使用病例对照方法研究了 DRD2 基因中的三个多态性与酒精依赖的遗传关联。酒精依赖通过 DSM-IV 标准确定，共招募了 90 名酗酒者和 60 名健康的无关年龄匹配的对照。计算比值比和置信区间以确定易感等位基因/基因型/单倍型赋予的风险。进行逻辑回归分析以将各种临床参数与基因型相关联，并研究 SNP 之间的成对相互作用。
该研究显示 DRD2 的-141C Ins 等位基因与酒精依赖显著相关，并且 TaqI A1 等位基因也有趋势。具有易感性-141C Ins 和 TaqI A1 等位基因的单倍型（-141C Ins-A-A1）似乎赋予了大约 2.5 倍的风险发展为酒精依赖。
该研究初步深入了解了印度男性对酒精依赖的遗传风险。DRD2 基因中的两个多态性，即-141C Ins/Del 和 TaqI A，可能在印度酒精性受试者中具有临床意义。
