title: Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Lee
authors.forename: Shiou-Lan
authors.initials: SL
authors.lastname: Chen
authors.forename: Shih-Heng
authors.initials: SH
authors.lastname: Chen
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Chu
authors.forename: Yun-Hsuan
authors.initials: YH
authors.lastname: Chang
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Lin
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Tzeng
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.forename: I Hui
authors.initials: IH
authors.lastname: Lee
authors.forename: Tzung Lieh
authors.initials: TL
authors.lastname: Yeh
authors.forename: Yen Kuang
authors.initials: YK
authors.lastname: Yang
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493593:DRD3 protein, human; D050637:Receptors, Dopamine D3