Association analyses reveal gender-specific associations of DAT1 40-bp VNTR and -839C/T polymorphisms with obsessive-compulsive disorder and obsessive-compulsive symptoms.

The dopamine transporter (DAT) is involved in dopamine signaling and distribution, controlling dopamine concentrations and contributing to several central nervous system disorders. The purpose of this study was to determine the association between two functional polymorphisms in DAT1 gene, the 40-base pair Variable Number of Tandem Repeats (VNTR) and the Single Nucleotide Polymorphism (SNP) -839C/T and obsessive-compulsive disorder (OCD) and/or its clinical features. To do so, 199 OCD patients and 201 healthy controls were genotyped using Polymerase Chain Reaction (PCR). Genotype distribution of both polymorphisms was in Hardy-Weinberg equilibrium. Although OCD and controls did not differ in terms of polymorphisms distribution, we observed that the presence of 10R-allele protected men of having OCD (P = 0.03). We also observed a significant association between the presence of 10R and checking in women (P = 0.02; OR = 3.14; 95%CI 1.08-9.11), and between the 9/9 genotype and neutralization in men (P = 0.04; OR = 3.38; 95%CI 1.03-11.11). Finally, the T-allele of -839C/T was significantly associated with the "obsession" score (P = 0.02; OR = 2.66; 95%CI 1.15-6.13). Our results demonstrate an important influence of dopaminergic pathways, particularly DAT1 polymorphisms, in OCD.