Crack Cocaine Users Show Differences in Genotype Frequencies of the 3′ UTR Variable Number of Tandem Repeats of the Dopamine Transporter Gene (DAT1/SLC6A3)

Abstract

Background: Due to the mechanism of action of the dopamine transporter (DAT) in drug addiction, the DAT1 gene is a potential candidate for molecular studies. This paper aims to compare the prevalence of allele and genotype frequencies created by the 3′ UTR variable number of tandem repeats (VNTR) of this gene between crack cocaine users and controls. Methods: A cross-sectional sample of 237 current adult crack cocaine abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics in southern Brazil and 205 community controls were compared. The subjects were evaluated using the Adult ADHD Self-Report Scale, the Mini-International Neuropsychiatric Interview - short version, and the Wechsler Intelligence Scale. DNA samples were genotyped for the DAT1 3′ VNTR. Results: Logistic regression analysis was performed to compare the frequency of the 10.10 genotype (the putative risk genotype) to those of other genotypes. A significant difference (p = 0.04, OR = 1.758, CI = 1.026-3.012) indicating an increased frequency of the 10.10 genotype in the cases (59.9%) compared to the controls (49.3%) was verified using clinical and demographic covariates. Conclusions: This is one of the first genetic association studies on crack cocaine users in the literature. The results suggest an influence of the DAT1 gene, namely the 3′ VNTR 10.10 genotype. However, more analyses will confirm and clarify its contribution as a possible risk factor for crack cocaine dependence.