Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder |
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Authors: | Sheng-Yu Lee Shiou-Lan Chen Shih-Heng Chen Chun-Hsien Chu Yun-Hsuan Chang Shih-Hsien Lin San-Yuan Huang Nian-Sheng Tzeng Po-Hsiu Kuo I Hui Lee Tzung Lieh Yeh Yen Kuang Yang Ru-Band Lu |
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Institution: | 1. Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan;2. Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan;3. Institute of Behavioral Medicine, National Cheng Kung University, Tainan, Taiwan;4. Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan;5. Addiction Research Center, National Cheng Kung University, Tainan, Taiwan;6. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;g Department of Public Health & Institute of Epidemiology, College of Public Health, National Taiwan University, Taiwan |
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Abstract: | ObjectivesBipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes.MethodsWe recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.ResultsLogistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P = 0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P = 0.027 and 0.006, respectively).ConclusionWe provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct. |
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Keywords: | BP Bipolar disorder SADS-L Schedule of Affective Disorder and Schizophrenia&mdash Lifetime HRSD Hamilton Rating Scale for Depression YMRS Young Mania Rating Scale |
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