The role of COMT functional and promoter polymorphisms in cocaine addiction : analysis of a large Brazilian case control sample

Genetic factors play a significant role in the development of cocaine addiction. Catechol-Omethyltransferase (COMT) is a major enzyme for the metabolism of dopamine, the neurotransmitter most directly related to the reinforcing properties of cocaine. In the present study, we genotyped three COMT SNPs [Val 108/158 Met (rs4680), rs737865, and rs165599] in a Brazilian sample comprised of 711 cocaine dependents and 862 healthy controls. Significant case-control differences were not observed for any individual SNP. Haplotype analyses showed that the haplotype comprised of alleles G-A-A of markers rs737865, rs4680 and rs165599, respectively, was over-represented in the cases (4%) compared to the controls (2%) (z=2.99; p=0.02). Moreover, when the markers rs737865/rs4680 were analyzed separately, the haplotype containing only alleles G-A was also significantly associated with cocaine abuse (z=3.46; p=0.006). 71 markers for genetic admixture analyses were also performed in the whole sample, and no difference was observed in case and controls, indicating that there is no significant population stratification in the sample. This study suggests that genetic variation in COMT might play a role in development of cocaine addiction in the Brazilian population.