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OPRM1基因A118G多态性及DRD4基因外显子3 VNTR多态性对饮酒后烟瘾的影响。

Influence of the A118G Polymorphism of the OPRM1 Gene and Exon 3 VNTR Polymorphism of the DRD4 Gene on Cigarette Craving After Alcohol Administration.

作者信息

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

机构信息

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;

出版信息

Nicotine Tob Res. 2016 May;18(5):632-6. doi: 10.1093/ntr/ntv136. Epub 2015 Jun 19.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

引言

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。

方法

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)。

结果

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。

结论

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。

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