The serotonin 2A receptor gene in alcohol dependence and tobacco smoking

Alcohol and nicotine abuse and dependence are multifactorial traits that frequently co-occur, where 80–90% of alcohol-dependent individuals who seek treatment smoke. Nicotine is the main compound of tobacco and one of its effects is to increase the release of serotonin. Variations in the serotonergic system may influence some aspects of smoking. The serotonin receptor gene HTR2A has been a candidate gene with some evidence for association with alcohol and nicotine dependencies. The polymorphism HTR2A A-1438G is a functional SNP, and the presence of the A allele increases the transcriptional activity of the gene. The aim of the present study was to test for possible associations between the A-1438G polymorphism in the serotonin receptor gene (HTR2A) with tobacco smoking combined or not with alcohol dependence. The polymorphic site was genotyped in three groups of European-derived Brazilians: individuals with co-occurrence of alcohol dependence and tobacco smoking (n = 113), non-alcoholic smokers (n = 120) and non-smoking controls (n = 115). A higher frequency of the A allele was observed in the two groups of smokers than in the non-smoking controls (x2 = 6.53, p = 0.04). Combining these groups in comparison with the control group, the difference is more significant (x2 = 6.45, p = 0.01). These results support previous evidence for association between HTR2A polymorphisms and substance use disorders.