The DRD3 Ser9Gly Polymorphism Predicted Metabolic Change in Drug-Naive Patients With Bipolar II Disorder.

Ting-Ting Chang, Shiou-Lan Chen, Yun-Hsuan Chang, Po-See Chen, Chun-Hsien Chu, Shih-Heng Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, Tzu-Yun Wang, Chia-Ling Li, Yi-Lun Chung, Tsai-Hsin Hsieh, I-Hui Lee, Kao-Ching Chen, Yen-Kuang Yang, Jau-Shyong Hong, Ru-Band Lu, Sheng-Yu Lee

Journal: Medicine 2017;95(24):e3488

PMID: 27310943

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Abstract

Patients with bipolar II disorder (BDII) have a higher prevalence rate of metabolic disturbance. Whether BDII itself, in addition to its current standard treatment, is a risk factor for metabolic syndrome warrants additional study. The dopamine receptor D3 (DRD3) gene, one of the candidate genes for BDII, is also involved in the dopaminergic system. We investigated whether it is related to changes in the metabolic indices of patients with BDII given 12 weeks of standard treatment.Patients with a first diagnosis of BDII (n = 117) were recruited. Metabolic profiles (cholesterol, triglycerides, fasting serum glucose, body mass index) were measured at baseline and at 2, 8, and 12 weeks. The genotype of the DRD3 Ser9Gly polymorphism (rs6280) was determined. Multiple linear regressions with generalized estimating equation methods were used.Seventy-six (65.0%) patients completed the 12-week intervention. Significant differences in triglyceride change were associated with the DRD3 Ser9Gly genotype (P = 0.03). Patients with the Ser/Ser genotype had significantly smaller triglyceride increases and a lower risk of developing metabolic syndrome than did those with the Ser/Gly+Gly/Gly genotype. However, the associations between the DRD3 Ser9Gly polymorphism with changes in triglyceride level become nonsignificant after correcting for multiple comparisons.We conclude that the DRD3 Ser9Gly polymorphism is nominally associated with changes in triglycerides and metabolic syndrome after 12 weeks of standard BDII treatment.

Address: From the Department of Psychiatry, E-Da Hospital, I-Shou University (T-TC); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung (S-LC); Department of Psychiatry, National Cheng Kung University Hospital, Tainan (S-LC, Y-HC, P-SC, T-YW, C-LL, Y-LC, T-HH, I-HL, K-CC, Y-KY, R-BL, S-YL); Department of Psychology, Asia University, Taichung (Y-HC); Institute of Allied Health, College of Medicine (Y-HC, R-BL); Department of Psychiatry, College of Medicine (P-SC, T-YW, I-HL, K-CC, Y-KY, R-BL, S-YL); Addiction Research Center (P-SC, R-BL); Institute of Molecular Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan (C-HC); Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, North Carolina (S-HC, J-SH); Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (S-YH, N-ST); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung (L-JW); Institute of Basic Medical Sciences, National Cheng Kung University, Tainan (Y-LC); Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin (Y-KY); Institute of Behavioral Medicine Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan (R-BL); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (R-BL); Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (S-YL).

DOI: 10.1097/MD.0000000000003488

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MeSH Terms: Bipolar Disorder, DNA, Dose-Response Relationship, Drug, Double-Blind Method, Female, GABA Agents, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Metabolic Syndrome, Polymorphism, Genetic, Receptors, Dopamine D3, Valproic Acid