Interaction of DRD2TaqI, COMT, and ALDH2 genes associated with bipolar II disorder comorbid with anxiety disorders in Han Chinese in Taiwan

It is hypothesized that dopaminergic genes—dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)—are associated with bipolar disorder (BP) and anxiety disorder (AD). Bipolar II (BP-II) is reported to be highly comorbid with AD. We examined whether interactions among these three genes are susceptibility factors in BP-II with AD (BP-II^+AD) and without AD (BP-II^−AD). In this study, we hypothesize that the interaction of the dopaminergic genes between BP-II^+AD and BP-II^-AD is significant different. We recruited 1260 participants: 495 with BP-II^−AD, 170 with BP-II^+AD, and 595 healthy controls without BP-II or AD. Genotyping was done using polymerase chain reactions plus restriction fragment length polymorphism analysis. Genotypic frequencies of the DRD2TaqIA, COMT, and ALDH2 polymorphisms between the two BP-II groups were nonsignificant. In logistic regression, the ALDH2 and DRD2TaqIA genes showed a main effect that was protective against BP-II^−AD (odds ratio [OR] = 0.497, p = 0.010, and OR = 0.415, p = 0.017, respectively). The interaction of DRD2TaqIA A1/A1 and ALDH2*1/*1 had a significant risk effect on the BP-II^−AD group (OR = 7.177, p < 0.001). However, the interaction of DRD2TaqIA A1/A1, ALDH2*1/*1, and COMTMet/Met&Val/Met become a weak protective factor against BP-II^−AD (OR = 0.205, p = 0.047). All of the significant results described above are found only in BP-II^−AD. This study supports the hypothesis the interaction of the dopaminergic genes between BP-II^+AD and BP-II^-AD is significant different,, and provides additional evidence that the DRD2TaqIA A1/A1, ALDH2*1/*1 and COMT genes interact in BP-II^−AD but not in BP-II^+AD.