Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

Abstract

Background Binge drinking is responsible for over half of all alcohol-related deaths, and results in significant health and economic costs to individuals and society. Knowledge of genetic aspects of this behavior, particularly as it emerges in young adulthood, could lead to improved treatment and prevention programs. Methods We have focused on the association of variation in neuronal nicotinic receptor subunit genes (CHRNs) in a cohort of 702 Hispanic and non-Hispanic White young adults who are part of the Social and Emotional Contexts of Adolescent Smoking Patterns (SECASP) study. Fifty-five single nucleotide polymorphisms covering the variation in five CHRNs (CHRNA4, CHRNB2, CHRNA2, CHRNB3A6 and CHRNA5A3B4) were studied. Results Frequency of binge drinking and other correlated alcohol consumption measures were significantly associated with SNPs in CHRNA4 (p-values ranged from 0.0003 to 0.02), but not with SNPs in other CHRNs. This association was independent of smoking status in our cohort. Conclusions Variants in CHRNA4 may contribute to risk for binge drinking in young adults in this cohort. Results will need to be confirmed in independent samples.

Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse

“…SNPs in other nAChR subunit genes have also been implicated in drug co-use, with CHRNB2 linked to initial subjective responses to both alcohol and tobacco (78), and the CHRNA6 - CHRNB3 gene complex linked to both smoking and heavy alcohol consumption (79,80). SNPs in the CHRNA5/A3/B4 gene cluster have been shown to be significant predictors of early initiation of tobacco or alcohol use (81–84) as well as associated with the frequency of adolescent binge drinking (85). …”

Genetic influences on adolescent behavior

“…A mu-opioid receptor gene, OPRM1 , has been implicated in both alcohol misuse (Miranda et al, 2010) and “antisocial drug dependence” (Corley et al, 2008). The nicotonic receptor family has also been implicated in antisocial behavior and drug use ( CHRNA2, Corley et al, 2008) and adolescent binge drinking ( CHRNA4 , Coon et al, 2014). Candidate gene studies, however, have not yielded the discriminatory power many researchers predicted (Dick et al, 2015).…”

Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism

“…109 In a recent study, using Hispanic and non-Hispanic white subjects from the Social and Emotional Contexts of Adolescent Smoking Patterns, revealed multiple polymorphisms of CHRNA4 were associated with a significantly elevated risk for adolescent binge drinking. 110 These authors reported that polymorphisms for other nAChR genes were not associated with this risk, which may be related to the ethnicity of the sample. Additional studies from the Nicotine Addiction Genetics consortium in Finland, reported a significant association between the CHRNB4 polymorphism rs11636753 and regular ethanol drinking with comorbidity for depression, which may have been sex dependent.…”