Association analysis of the dopamine transporter (DAT1)-67A/T polymorphism in bipolar disorder

An imbalance in the dopaminergic system in humans has been hypothesized to contribute to the pathogenesis of a number of psychiatric illnesses, including bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. We performed a case/control study on the DAT1 (HUGO approved symbol SL6A3) gene core promoter polymorphism -67A/T to analyze the possible association of either allele of this polymorphism with bipolar disorder. The allele and genotype frequencies of the polymorphism were studied in 136 patients and 163 controls, which were matched on the basis of sex, age, and ethnicity. The genotype frequencies in the patients group were as follows: AA 30.9%; AT 55.1%; TT 14% versus the genotype frequencies in the control group: AA 49%; AT 41.8%; TT 9.2% [chi2 = 10.3, df = 2, OR = 2.15 (95% CI 1.34-3.47, P < or = 0.006]. The T-allele of the -67A/T polymorphism revealed a approximately 1.4-fold excess in the patients group comparing with the controls (P < or = 0.003). For the first time, these findings provide tentative evidence of the contribution of the DAT1 gene core promoter polymorphism to the etiopathophysiology of bipolar disorder at least in the Iranian population that we have studied. Interestingly, no allelic or genotype association was observed in the female patients (P < or = 0.6 and P < or = 0.7, respectively). Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.