Lechner William V, Knopik Valerie S, McGeary John E, Spillane Nichea S, Tidey Jennifer W, McKee Sherry A, Metrik Jane, Leventhal Adam M, Rohsenow Damaris J, Kahler Christopher W
Center for Alcohol and Addiction Studies, Brown University School of Public Health, Providence, RI;
Division of Behavioral Genetics, Rhode Island Hospital, Providence, RI; Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI;
Nicotine Tob Res. 2016 May;18(5):632-6. doi: 10.1093/ntr/ntv136. Epub 2015 Jun 19.
The current study examined whether the presence of the G allele of the A118G polymorphism of the OPRM1 gene (rs1799971) and the long allele of exon 3 VNTR polymorphism of the DRD4 gene moderate the effect of alcohol administration on urge to smoke. These polymorphisms have been associated with greater alcohol induced-urge to drink. Urge to drink and alcohol consumption increase urge to smoke. Therefore, these polymorphisms may also sensitize urge to smoke after alcohol consumption.
Individuals smoking 10-30 cigarettes per day and reporting heavy drinking were recruited from the community. Caucasians (n = 62), 57.3% male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design study. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. A118G genotype, exon 3 VNTR genotype, and urge to smoke (baseline and three times after receiving alcohol) were assessed.
G allele carriers showed greater urge to smoke across all assessments. Additionally, a significant interaction indicated that G carriers, compared to homozygotes (AA), evinced a significantly greater increase in urge to smoke after high dose alcohol relative to placebo. The interaction between condition, DRD4 polymorphism, and time was not significant.
Presence of G allele of the A118G polymorphism of the OPRM1 gene may lead to greater increases in urge to smoke after a high dose of alcohol. Pharmacotherapies targeted to opiate receptors (eg, naltrexone) may be especially helpful in aiding smoking cessation among G carriers who are heavy drinkers.
本研究探讨了阿片受体μ1基因(OPRM1)A118G多态性(rs1799971)的G等位基因以及多巴胺D4受体基因(DRD4)第3外显子可变数目串联重复序列(VNTR)多态性的长等位基因是否会调节饮酒对吸烟欲望的影响。这些多态性与更高的酒精诱导饮酒欲望有关。饮酒欲望和酒精摄入量会增加吸烟欲望。因此,这些多态性也可能使饮酒后吸烟欲望更加敏感。
从社区招募每天吸烟10 - 30支且报告大量饮酒的个体。62名高加索人参与了这项为期三阶段的、受试者内重复测量设计研究,其中男性占57.3%,平均年龄39.2岁。参与者分别接受安慰剂、0.4 g/kg或0.8 g/kg剂量的酒精。评估了A118G基因型、第3外显子VNTR基因型以及吸烟欲望(基线和饮酒后三次)。
在所有评估中,G等位基因携带者表现出更高的吸烟欲望。此外,一个显著的交互作用表明,与纯合子(AA)相比,G等位基因携带者在高剂量酒精相对于安慰剂的情况下,吸烟欲望显著增加。条件、DRD4多态性和时间之间的交互作用不显著。
OPRM1基因A118G多态性的G等位基因可能导致高剂量酒精后吸烟欲望的更大增加。针对阿片受体的药物治疗(如纳曲酮)可能对帮助大量饮酒的G等位基因携带者戒烟特别有帮助。