Association Study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A Polymorphisms with Alcohol Dependence in a Population from Northeastern Brazil

Background: Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD. The aim of this search was to test the association of the SLC6A3 40 bp-VNTR and DRD2/ANKK1 Taq1A single nucleotide polymorphism (SNP), a transporter and receptor of the dopaminergic system, with AD through a study in a population of northeastern Brazil.

Methods: The study design was a case-control that included 227 males of northeastern Brazil (113 alcoholics and 114 controls). Alcoholics were classified according to the DSM-IV criteria for AD and controls were subjects who had nonalcohol problems or who never drank. Genotyping was detected through polymerase chain reaction (PCR) for SLC6A3 40 bp-VNTR and RFLP-PCR for DRD2/ANKK1 Taq1A, and subsequent electrophoresis on a 2% agarose gel. The distribution of allele and genotype frequencies and association of polymorphisms with AD were assessed by chi-square, Fisher's exact test, and odds ratio (OR) with a confidence interval of 95% and significance p < 0.05. Data were analyzed on BioEstat 5.3 software.

Results: The SLC6A3 40 bp-VNTR was associated with AD, allelic, and genotypic frequencies were significantly different, respectively (A9 vs. A10: OR = 1.88; p = 0.01; A9/A9 vs. A10/A10: OR = 6.25; p = 0.02; A9/A9 vs. A9/A10 + A10A10: OR = 5.44; p = 0.03). However, there was no statistically significant difference when the allelic (p = 0.10) and genotypic (p > 0.05) frequencies for DRD2/ANKK1 Taq1A were compared.

Conclusions: These findings suggest that A9 allele and A9/A9 genotype of the SLC6A3 40 bp-VNTR are involved in the vulnerability to AD in the population studied. However, for the DRD2/ANKK1 SNP does not present contributions to the development of AD.