Abstract
BackgroundClock 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.MethodsData 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.ResultsIndividuals 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.ConclusionsThese 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.
Highlights
Alcohol use disorders (AUDs) are regarded as one of the most severe public health problems worldwide, being the leading cause of a wide variety of morbidity and mortality conditions in many developed countries
Given the role of clock genes and stress in heavy alcohol use, the aim of the present study was twofold: 1) to extend previous findings suggesting an association of PER2 rs56013859 genotype with drinking patterns in an epidemiological cohort study of young adults from a high-risk sample, and 2) to examine a role for this genotype in moderating the effect of exposure to severe stressful life events on hazardous drinking
The present study provides further evidence, suggesting a possible role for allelic variation of the PER2 gene in alcohol drinking in humans
Summary
Alcohol use disorders (AUDs) are regarded as one of the most severe public health problems worldwide, being the leading cause of a wide variety of morbidity and mortality conditions in many developed countries. The psychoactive effects of alcohol are mediated through its influence on different functional systems in the brain, including the dopamine, serotonin, gamma-aminobutyric acid, glutamate, and opioid peptide systems Another system whose involvement in the etiology and continuation of alcohol abuse has recently been proposed is the circadian clock mechanism [6]. Circadian rhythmicity was found to be influenced by substance use, in general, and alcohol use, in particular, notably heavy use [9]. This becomes apparent in severe disorganizations of physiological clock systems, such as sleep, body temperature or blood pressure during chronic alcohol abuse, dependence and withdrawal, with these disorganizations being based on altered expression of the clock genes. 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
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