Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder.

ABSTRACT

Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5-HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.