Gender dimorphism in the DAT1 -67 T-allele homozygosity and predisposition to bipolar disorder.

Linkage and association studies implicate the dopamine transporter gene (DAT1) in the etiopathophysiology of bipolar disorder. We have recently reported the association between the DAT1 core promoter -67A/T polymorphism and this disorder in a sample of Iranian patients. For the first time, these data support sex dimorphism in the homozygosity for the -67 T-allele between male and female affected cases. The present study was undertaken with a larger sample size of cases (N=240) and controls (N=213) to determine whether there is consistent difference between male and female patients and homozygosity for this allele. The results confirm and strengthen our preliminary observation that homozygosity for the T-allele is a predisposing factor in male patients, but not in females (chi2=8.825, df=1, p=0.003). Moreover, Hardy-Weinberg disequilibrium was observed in the female cases studied (chi2=12.9, df=1, p=0.0003), which may reflect the underlying biology. These findings imply gender dimorphism with respect to the DAT1 -67 alleles and susceptibility to disease.