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PER2 基因型和生活应激事件与青年饮酒的关联。

Association of PER2 genotype and stressful life events with alcohol drinking in young adults.

机构信息

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

出版信息

PLoS One. 2013;8(3):e59136. doi: 10.1371/journal.pone.0059136. Epub 2013 Mar 22.

Abstract

BACKGROUND

Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking.

METHODS

Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview.

RESULTS

Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress.

CONCLUSIONS

These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.

摘要

背景

时钟基因控制着昼夜节律,并影响酒精对生理系统的作用。暴露于严重的负面生活事件与大量饮酒和昼夜节律紊乱有关。本研究的目的是:1)扩展先前的研究结果,该结果表明 PER2 基因的单核苷酸多态性单倍型标签与饮酒模式有关,2)检验该基因与生活压力相互作用在危险饮酒中的可能作用。

方法

数据是作为一项关于自出生以来早期风险因素结果的流行病学队列研究的一部分收集的。在 19 岁时,268 名年轻成年人(126 名男性,142 名女性)接受了 PER2 rs56013859 基因分型,并接受了为期 45 天的酒精时间线随访访谈和酒精使用障碍识别测试(AUDIT)。生活压力通过问卷评估过去四年中报告的严重负面生活事件的数量,并通过访谈进行验证。

结果

与主要 A 等位基因的纯合子相比,rs56013859 的次要 G 等位基因个体的饮酒量较少,仅在 72%的天数内饮酒。此外,还出现了基因 x 环境相互作用(p=0.020)。在低压力条件下,基因型没有影响,但是当暴露于高压力时,G 等位基因携带者的危险饮酒程度低于 A 等位基因纯合子。

结论

这些发现可能表明昼夜节律基因 PER2 既在年轻人的饮酒模式中起作用,又在调节严重生活压力对有经验饮酒者危险饮酒的影响方面起作用。但是,鉴于多次测试的可能负担,所用措施的性质以及相互作用的名义证据,在得出确定的结论之前,需要进行复制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f126/3606431/b9ee94513959/pone.0059136.g001.jpg

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