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

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Abstract

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.

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Acknowledgments

This study was supported in part by grant DOH95-TD-M-113055 (to Ru-Band Lu) from the Taiwan Ministry of Health; grants NHRI-EX97-9738NI, NHRI-EX98-9738NI, and NHRI-EX99-9738NI (to Ru-Band Lu) from the Taiwan National Health Research Institutes; grants NSC98-2627-B-006–017, NSC99-2627-B-006–015, and NSC100-2627-B-006–013 (to Ru-Band Lu); grant NSC100-2314-B-006–048-MY3 (to Sheng-Yu Lee) from the Taiwan National Science Council; and by a grant from the National Cheng Kung University Project to Promote Academic Excellence & Develop World Class Research Centers (to Ru-Band Lu). However, the above institutions had no further role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.

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The authors declare that they have no conflicts of interest concerning this article.

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Authors and Affiliations

  1. Institute of Behavioral Medicine, Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan

    Ming-Chuan Hu, Tzu-Yun Wang & Ru-Band Lu

  2. Institute of Allied Health Sciences, National Cheng Kung University, Tainan, Taiwan

    Yun-Hsuan Chang & Ru-Band Lu

  3. Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yun-Hsuan Chang, Shih-Heng Chen, Chun-Hsien Chu, Chen-Lin Wang, I Hui Lee, Po See Chen, Yen Kuang Yang & Ru-Band Lu

  4. Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan

    Tzu-Yun Wang, I Hui Lee, Yen Kuang Yang & Ru-Band Lu

  5. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Sheng-Yu Lee

  6. Department of Psychiatry, Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan

    Tzu-Yun Wang

  7. Department of Neurology, School of Medical University, Kaohsiung, Taiwan

    Shiou-Lan Chen

  8. Center for Neuropsychiatric Research, National Health Research Institute, Miaoli, Taiwan

    Ru-Band Lu

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  1. Ming-Chuan Hu
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Hu, MC., Lee, SY., Wang, TY. et al. Interaction of DRD2TaqI, COMT, and ALDH2 genes associated with bipolar II disorder comorbid with anxiety disorders in Han Chinese in Taiwan. Metab Brain Dis 30, 755–765 (2015). https://doi.org/10.1007/s11011-014-9637-x

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