Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, The Netherlands.
Addict Biol. 2013 Mar;18(2):344-56. doi: 10.1111/j.1369-1600.2012.00438.x. Epub 2012 Apr 17.
Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.
遗传因素和儿童期逆境经历导致对酒精依赖的易感性。然而，关于特定基因和逆境经历之间相互作用的经验数据很少。COMT Val158Met 和 DRD2/ANKK1 Taq1A 基因型被认为既影响应激敏感性，又影响酒精依赖的风险。本研究检验了 COMT Val158Met 和 DRD2/ANKK1 Taq1A 遗传变异与儿童期逆境经历相互作用，预测酒精依赖的假设。男性戒酒酒精依赖患者（n = 110）和年龄匹配的健康男性对照（n = 99）被基因分型 COMT Val158Met 和 DRD2/ANKK1 Taq1A 基因型。使用三个自我报告问卷测量儿童期逆境事件。将酒精依赖严重程度、发病年龄和酒精依赖持续时间作为次要结局进行分析。统计分析包括逻辑回归分析和方差分析。酒精依赖患者报告儿童期逆境增加。童年逆境与 COMT Val158Met 基因型的相互作用显著增加了预测模型。这种基因-环境相互作用在次要结局测量的分析中得到了证实，即酒精依赖严重程度、发病年龄和酒精依赖持续时间。DRD2/ANKK1 Taq1A 基因型与酒精依赖无关，也不能与童年逆境相互作用预测酒精依赖。本研究为酒精依赖中的基因-环境相互作用提供了证据，其中个体对儿童期逆境经历的敏感性受 COMT 基因型调节。低活性 Met 等位基因的暴露携带者比 Val 等位基因纯合子发生严重酒精依赖的风险更高。
