Subjective Response to Alcohol Among Alcohol-Dependent Individuals: Effects of the Mu-Opioid Receptor (OPRM1) Gene and Alcoholism Severity
Subjective Response to Alcohol Among Alcohol-Dependent Individuals: Effects of the Mu-Opioid Receptor (OPRM1) Gene and Alcoholism Severity
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DOI：
10.1111/j.1530-0277.2012.01916.x
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发表时间：
2013-01-01
影响因子：
3.2
通讯作者：
Miotto, Karen
中科院分区：
文献类型：
--
作者：
Ray, Lara A.;Bujarski, Spencer;Miotto, Karen
背景对酒精的主观反应已被视为酒精中毒风险的标志。μ阿片受体（OPRM 1）基因的A118 G单核苷酸多态性（SNP）先前已与重度饮酒者对酒精的主观反应相关。本研究旨在通过研究OPRM 1基因型对酒精依赖个体样本中酒精反应的影响来扩展文献。本研究的第二个目的是研究酒精中毒的严重程度作为对酒精的主观反应的预测。方法在实验室对295名非寻求治疗的问题饮酒者进行酒精依赖的临床维度评估。在前瞻性基因分型后，43名酒精依赖个体在2种基因型条件下（AA，n = 23和AG/GG，n = 20）被随机分配至2个静脉输注阶段：1个酒精（目标呼气酒精浓度= 0.06 g/dl）和1个生理盐水。在两次输注中均进行了对酒精主观反应的测量。结果与A等位基因纯合子相比，酒精依赖G等位基因携带者报告了更大的酒精诱导的刺激，活力和积极的情绪。基因型对酒精诱导的镇静或渴望没有影响。有一个统计趋势水平的严重程度志酒精相互作用，使个人在更高的严重程度报告更大的酒精引起的紧张减少。结论在酒精依赖患者中，OPRM 1基因型调节酒精的享乐效应，但不调节酒精的镇静和不愉快效应。结果进行了讨论，根据临床神经科学框架酒精中毒。
Background Subjective response to alcohol has been examined as a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1) gene has been previously associated with subjective response to alcohol in heavy drinkers. This study seeks to extend the literature by examining the effect of OPRM1 genotype on responses to alcohol in a sample of alcohol-dependent individuals. A secondary aim of this study is to examine alcoholism severity as a predictor of subjective responses to alcohol. Methods Nontreatment seeking problem drinkers (n = 295) were assessed in the laboratory for clinical dimensions of alcohol dependence. Following prospective genotyping, 43 alcohol-dependent individuals across the 2 genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to 2 intravenous infusion sessions: 1 of alcohol (target breath alcohol concentration = 0.06 g/dl) and 1 of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. Results Alcohol-dependent G-allele carriers reported greater alcohol-induced stimulation, vigor, and positive mood, as compared to A-allele homozygotes. There was no genotype effect on alcohol-induced sedation or craving. There was a statistical trend-level severity Chi alcohol interaction such that individuals at higher levels of severity reported greater alcohol-induced tension reduction. Conclusions These results support the hypothesis that OPRM1 genotype moderates the hedonic effects of alcohol, but not the sedative and unpleasant effects of alcohol, in a sample of alcohol-dependent patients. Results are discussed in light of a clinical neuroscience framework to alcoholism.