Association of the neuronal nicotinic receptor β2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine

Abstract

Nicotine addiction and alcohol dependence are highly comorbid disorders that are likely to share overlapping genetic components. We have examined two neuronal nicotinic receptor subunit genes (CHRNA4 and CHRNB2) for possible associations with nicotine and alcohol phenotypes, including measures of frequency of use and measures of initial subjective response in the period shortly after first using the drugs. The subjects were 1,068 ethnically diverse young adults participating in ongoing longitudinal studies of adolescent drug behaviors at the University of Colorado, representing both clinical and community samples. Analysis of six SNPs in the CHRNA4 gene provided modest support for an association with past 6 month use of alcohol in Caucasians (three SNPs with P < 0.08), but no evidence for an association with tobacco and CHRNA4 was detected. However, a SNP (rs2072658) located immediately upstream of CHRNB2 was associated with the initial subjective response to both alcohol and tobacco. This study provides the first evidence for association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes, and suggests that polymorphisms in CHRNB2 may be important in mediating early responses to nicotine and alcohol.

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

“…A study of Korean adult alcoholics revealed an association with CHRNA4 , in addition to significant effects of several other candidate genes (Kim et al, 2004). Focusing on the subjective responses to nicotine and alcohol, Ehringer et al (2007) showed a modest CHRNA4 association with alcohol (but not nicotine) in Caucasian adolescents recruited from substance use treatment centers, the criminal justice system, and community-based studies. Subsequent studies from this research group using this cohort have gone on to reveal modest associations between CHRNA4 and adolescent nicotine dependence (Kamens et al, 2013).…”

Association of candidate genes with antisocial drug dependence in adolescents

“…Two studies have reported associations between CHRNA4 haplotypes and smoking-related phenotypes (Feng et al, 2004;Li et al, 2005). Ehringer et al (2007) found an association between SNPs in the CHRNA4 gene and current smoking and between both smoking and alcohol subjective response phenotypes and a SNP in the CHRNB2 gene. The CHRNB3 and CHRNB5 genes have also emerged as strong candidates for nicotine dependence in two recent reports of a genome wide association and a high-throughput candidate gene survey (Bierut et al, 2007;Saccone et al, 2007).…”

“…The CHRNB3 and CHRNB5 genes have also emerged as strong candidates for nicotine dependence in two recent reports of a genome wide association and a high-throughput candidate gene survey (Bierut et al, 2007;Saccone et al, 2007). Additionally, CHRNB3 has been associated with alcohol abuse in males (Zeiger et al, 2007).…”

“…These candidates were chosen for functional reasons or because they have been associated with SUD or substancerelated behaviors. Genes included are involved with four major neurotransmitter systems in the brain: dopaminergic (Limosin et al, 2005;Chen et al, 2005), serotonergic (Hopfer et al, 2005;Curtis, 2004), GABAergic (Radel et al, 2004;Nishiyama et al, 2005;Parsian et al, 1998), and cholinergic (Ehringer et al, 2007;Beirut et al, 2007;Saccone et al, 2007). A matched case-control design (matched on ethnicity and birth year) was utilized to test the extent to which individual SNPs predicted case/control status using within-gene correction for multiple SNPs.…”

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

“…Furthermore, a recent study investigated the relation between CHRNB2 and initial subjective responses to smoking (e.g. feeling dizzy or nauseous after smoking) and identified one SNP (rs2072658) located upstream of the CHRNB2 gene that was associated with an increased response to the negative effects of smoking, whereas another SNP (rs2072660) located in the 3' UTR was associated with a reduced subjective response to the negative effects of smoking [40]. Thus, the results from these studies suggest that polymorphisms in CHRNB2 may also modulate smoking-related behaviors.…”