Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder

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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Abstract

Objectives: Bipolar 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. Methods: We 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. Results: Logistic 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). Conclusion: We 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.

Original languageEnglish
Pages (from-to)382-387
Number of pages6
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume39
Issue number2
DOIs
Publication statusPublished - 2012 Dec 3

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biological Psychiatry

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    Lee, S. Y., Chen, S. L., Chen, S. H., Chu, C-H., Chang, Y. H., Lin, S. H., Huang, S. Y., Tzeng, N. S., Kuo, P. H., Lee, I-H., Yeh, T. L., Yang, Y-K., & Lu, R-B. (2012). Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 39(2), 382-387. https://doi.org/10.1016/j.pnpbp.2012.07.015