Taq1A polymorphism in patients with bipolar disorder: A candidate gene study based on the dopamine hypothesis

This study explored the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ) by examining the associations between the two disorders and single nucleotide polymorphisms (SNPs) involved in the dopamine signaling system. This was a case-controlled, exploratory, and multicenter study. A total of 1048 patients with BD (495 male; mean age, 49.6 ​± ​15.0 years), 2106 patients with SZ (1159 male, 49.6 ​± ​15.0 years), and 2240 healthy controls (HCs) (917 male, 42.3 ​± ​14.2 years) were included, and all the volunteers were Japanese. SNPs at tyrosine hydroxylase rs10770141 ​C-824T, catechol-O-methyltransferase rs4680 ​G/A(Val158Met), dopamine receptor D2 gene (DRD2) rs1799732 -141C Ins/Del, and DRD2/ANKK1 (Taq1A) rs1800497 ​C/T were examined. Binomial logistic regression analyses were performed to analyze the four SNPs, age, and sex. C allele and heterozygous CT in Taq1A were associated with an increased risk of BD. A comparison of the BD and HC groups revealed a significant association between heterozygous CT in Taq1A and BD in female participants. Heterozygous CT in Taq1A showed a significant association with BD as compared to SZ. DRD2 Taq1A polymorphism (CT heterozygotes) is associated with a high risk of BD in the Japanese population, particularly in females. DRD2 genetic predisposition in the dopamine signaling system and sex-specific factors may be associated with the pathophysiology of BD.