The interaction between BDNF and DRD2 in Bipolar II disorder but not in bipolar I disorder

Bipolar I (BP-I) and bipolar II (BP-II) disorders are the two most common subtypes of bipolar disorder. However, most studies have not differentiated bipolar disorder into BP-I and BP-II groups, for which the underlying etiology differentiating these two subtypes remains unclear. The genetic association between both subtypes is essential for improving our understanding. The dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1), one of the dopaminergic pathways, as well as the brain-derived neurotrophic factor (BDNF) gene, were reported as candidate genes in the etiology of bipolar disorder. Therefore, we examined the contribution of the BDNF and DRD2/ANKK1 genes and their interaction to the differentiation of BP-I and BP-II. Seven hundred ninety-two participants were recruited: 208 with BP-I, 329 with BP-II, and 255 healthy controls. The genotypes of the BDNF and DRD2/ANKK1 Taq1A polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism predicted BP-II patients. The significant interaction effect for the Val/Val genotype of the BDNF Val66Met polymorphism and A1/A2 genotype of DRD2/ANKK1 Taq1A polymorphism was found only in BP-II patients. We provide initial evidence that the BDNF Val66Me and DRD2/ANKK1 Taq1A polymorphisms interact only in BP-II disorder and that BP-I and BP-II are genetically distinct.