Association of nAChR gene haplotypes with heavy alcohol use and body mass

Co-occurring alcohol and nicotine dependence is common, as is alcohol use disorder and overeating. However, major risk genes for these disorders need to be identified. Certain subtypes of the nicotinic acetylcholine receptors in the ventral tegmental area (a reward node) have preclinically been shown to be important for alcohol reward. Therefore the aim was to investigate nicotine receptor subunit genes in a haplotype study of alcohol use. This study includes a Spanish population (n=417) of three groups based on their alcohol consumption; abstainers (n=142), moderate (<280 g/week, n=111) and heavy drinkers (>280 g/week, n=164). 20 tag SNPs in five nicotine receptor subunit genes (CHRNA3, 4, and 6; CHRNB2 and 3) were genotyped and analysed for single marker and haplotype associations. Two haplotypes of the CHRNA6 (CCCC and TCGA) were associated with heavy alcohol consumption (p=0.004 and p=0.035 respectively) and with increased alcohol intake (p=0.004) for the CCCC haplotype compared to non-carriers of these haplotypes. Moreover, one haplotype of the CHRNA4 (GGTG) was associated with increased body weight as compared to non-carriers of this haplotype, especially in the heavy consumers of alcohol (p=0.004).The present findings are the first to disclose a haplotype association between the CHRNA6 gene and heavy alcohol use as well as an association of the CHRNA4 gene with increased body mass in heavy consumers of alcohol. Taken together with previous preclinical data, this targets the nicotinic acetylcholine receptors for development of novel treatment strategies of addictive behaviours, and, more specifically, of a subgroup of individuals with co-morbid alcohol use disorder and overeating.