Several lines of evidence support mitochondrial dysfunction in bipolar disorder. Elevated calcium level in platelets is reported in this disease. To verify mitochondrial DNA (mtDNA) haplogroups characteristic to bipolar disorder, we sequenced mtDNA of seven regions and performed haplogroup analysis in 195 patients with bipolar disorder and 255 controls. They belonged to 16 major mtDNA haplogroups, A, B4, B5, C, D4, D5, F, G, M7, M8, M9, M10-12, N9a, N9b, Y, and Z. The logistic regression analysis revealed that the haplogroup N9a was over-represented in bipolar disorder. We also performed a case-control study for two functional mtDNA polymorphisms, mtDNA5460G > A and 12358A > G, that altered intracellular calcium dynamics. While the mtDNA5460G > A polymorphism was not associated with bipolar disorder, the mtDNA12358A > G polymorphism was associated with bipolar disorder in 199 patients with bipolar disorder and 260 controls. However, this association was not replicated in an independent sample set. Possible significances of these findings are discussed.
2008 Wiley-Liss, Inc.