Circadian Clock Gene Polymorphisms in Alcohol Use Disorders and Alcohol Consumption
Circadian Clock Gene Polymorphisms in Alcohol Use Disorders and Alcohol Consumption
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DOI：
10.1093/alcalc/agq035
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发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Partonen, Timo
中科院分区：
文献类型：
--
作者：
Kovanen, Leena;Saarikoski, Sirkku T.;Partonen, Timo
目的：生物钟基因参与药物诱导行为的形成，并调节成瘾的神经传递途径。我们的目的是研究生物钟基因多态性是否易患酒精依赖或滥用或其他酒精相关特征。研究方法：研究样本包括512名酒精依赖或酒精滥用者（根据精神疾病诊断和统计手册，第四版（DSM-IV））和511名年龄和性别匹配的对照组。这一基于人群的样本来自一个队列（n = 7415），代表芬兰30岁及以上的一般人群。共检测了与昼夜节律起搏系统相关的19个基因的42个单核苷酸多态性。结果如下：ARNTL rs6486120 T+等位基因状态（P = 0.0007，q = 0.17）、ADCYAP 1 rs 2856966 GG基因型（P = 0.0006，q = 0.17）和VIP CC单倍型（rs3823082-rs688136）（P = 0.0006）与社交饮酒对照中的饮酒量相关。ARNTL 2 GT单倍型（rs7958822-rs 4964057）与酒精滥用诊断相关（P = 0.0013）。DRD 2和NPY与酒精依赖相关的早期发现得到了支持：DRD 2/ANKK 1 Taq 1A（1）增加（P = 0.04），NPY Pro 7降低（P = 0.01）酒精依赖的风险。结论：ARNTL、ARNTL 2、VIP和ADCYAP 1对酒精使用或滥用有影响。DRD 2和NPY在酒精依赖中的作用也得到了支持。
Aims: Circadian clock genes are involved in the development of drug-induced behaviors and regulate neurotransmission pathways in addiction. Our aim was to study whether circadian clock gene polymorphisms predispose to alcohol dependence or abuse or other alcohol-related characteristics. Methods: The study sample comprised of 512 individuals having alcohol dependence or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)) and their 511 age- and sex-matched controls. This population-based sample was drawn from a cohort (n = 7415), representative of the Finnish general population aged 30 and over. Altogether 42 single-nucleotide polymorphisms of 19 genes related to the circadian pacemaker system were genotyped. Results: ARNTL rs6486120 T+ allelic status (P = 0.0007, q = 0.17), ADCYAP1 rs2856966 GG genotype (P = 0.0006, q = 0.17) and VIP CC haplotype (rs3823082-rs688136) (P = 0.0006) were suggestively associated with alcohol consumption in socially drinking controls. ARNTL2 GT haplotype (rs7958822-rs4964057) associated suggestively with alcohol abuse diagnosis (P = 0.0013). Earlier findings on the associations of DRD2 and NPY with alcohol dependence were supported: DRD2/ANKK1 Taq1A(1) increased (P = 0.04) and NPY Pro7 decreased (P = 0.01) the risk of alcohol dependence. Conclusions: ARNTL, ARNTL2, VIP and ADCYAP1 were indicated as having influence on alcohol use or abuse. The role of DRD2 and NPY on alcohol dependence was also supported.