LAUSR

Background Crack cocaine is a highly addictive substance and this dependence has a significant prevalence worldwide, especially in Brazil. Several factors are involved on crack cocaine dependence, and heritability estimates have highlighted the influence of genetic variants in the dependence susceptibility. Previous studies have shown that genetic variants in nicotine receptor genes are not only associated with nicotine abuse, but also with cocaine dependence. Our aim was to investigate the effects of polymorphisms in the nicotinic receptor alpha 5 gene - CHRNA5 - on crack cocaine dependence. Methods Three hundred crack cocaine users and six hundred and thirty-three healthy controls were enrolled in this study. The sample was composed of white Brazilians with European descent. Diagnoses and clinical assessments were performed according to DSM-IV criteria. The Addiction Severity Index - 6 (ASI-6) was used to assess the severity of dependence. Three polymorphisms were analyzed in the CHRNA5 gene (rs588765, rs16969968, and rs514743). Logistic regression models and general linear models were used to evaluated the effect of SNPs on crack cocaine addiction and severity of dependence, respectively. Results Significant effects were found for two polymorphisms. Genotypes TT-rs588765 and AA-rs16969968 were associated with reduced risk to crack cocaine dependence (OR=0.581, P=0.037; OR=0.532, P=0.009, respectively). However, only a trend towards association for rs514743 was detected (TT, OR=0.571, P=0.065). Analyses regarding severity of dependence did not reveal any significant association between SNPs and scores generated by ASI-6. Discussion We replicated previous findings regarding the influence of CHRNA5 gene on cocaine addiction. Notwithstanding, studies have demonstrated that rs16969968 apparently presents opposite effects in nicotine and crack/cocaine addictions. Our perspectives include increasing sample size and further explore other aspects possibly involved with addiction, such as age of first use and psychiatric comorbidities. Potential implications of these genetic factors should be more explored in future studies.