Association of PER2 Genotype and Stressful Life Events with Alcohol Drinking in Young Adults

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.

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

“…Mutations in the clock genes per1 and per2 increase alcohol intake in mice following social defeat (Dong et al, 2011, Gamsby et al, 2013, Spanagel et al, 2005). Furthermore, per1 and per2 mutations in young adults are correlated with increased sensitivity to stress and heavy alcohol drinking (Blomeyer et al, 2013, Spanagel et al, 2005). Thus, phylogenetically conserved molecular mechanisms exist that could potentially link age-related changes in the circadian system and increased alcohol sensitivity.…”

Clock genes × stress × reward interactions in alcohol and substance use disorders

“…In addition to the above-mentioned rodent studies, several human genetic studies have also revealed associations of certain polymorphisms of several clock genes with AUD and SUDs (Blomeyer et al, 2013; Brower, Wojnar, Sliwerska, Armitage, & Burmeister, 2012; Comasco et al, 2010; Dong et al, 2011; Kovanen et al, 2010; Malison, Kranzler, Yang, & Gelernter, 2006; Sjoholm et al, 2010; Spanagel et al, 2005; Surovtseva, Kudryavtseva, Voronina, Pronin, & Filipenko, 2012; Wang et al, 2012; Zou et al, 2008). Although associations of certain clock gene variants and AUD and SUDs could not always be replicated (Malison et al, 2006; Surovtseva et al, 2012), in sum these genetic studies link clock gene function and addictive behavior in humans (Partonen, 2015).…”

“…The implication of the Per2 gene in controlling drinking behavior has been further extended to stress effects. The same SNP of the hPer2 gene also moderates the impact of severe stress on alcohol abuse (Blomeyer et al, 2013). Experienced alcohol users carrying a G allele haplotype at the same SNP rs56013859 and who experienced early young adult life stressful events (i.e., death of a loved one or relationship breakup) were found to drink to a lesser extent than homozygotes carrying the major A allele.…”

Gene-Environment Interplay and Substance Use: A Review of Recent Findings

“…Using mouse models, researchers have found that circadian rhythmicity, which governs how an individual adapts to their internal and external environment, shapes the rewarding effects of alcohol use [53]. Several studies have found links between clock genes and alcohol dependence in humans [54,55] and in a sample of 268 young adults, the association between stressful life events and alcohol use was shown to be stronger among individuals who carried the AA genotype of the period circadian clock (PER) gene than among G allele carriers [56].…”