The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
Further support for association of the mitochondrial complex I subunit gene NDUFV2 with bipolar disorder
Version of Record online: 10 JAN 2008
Volume 10, Issue 1, pages 105–110, February 2008
How to Cite
Xu, C., Li, P. P., Kennedy, J. L., Green, M., Hughes, B., Cooke, R. G., Parikh, S. V. and Warsh, J. J. (2008), Further support for association of the mitochondrial complex I subunit gene NDUFV2 with bipolar disorder. Bipolar Disorders, 10: 105–110. doi: 10.1111/j.1399-5618.2008.00535.x
- Issue online: 10 JAN 2008
- Version of Record online: 10 JAN 2008
- Received 21 July 2006, revised and accepted for publication 26 February 2007
- bipolar disorder;
- calcium homeostasis;
- haplotype analysis;
- single nucleotide polymorphisms;
Background: The nuclear-encoded mitochondrial complex I subunit gene, NDUFV2, has been implicated in the pathogenesis of bipolar disorder (BD) in Japanese by virtue of association of variants in its promoter with BD and decreased NDUFV2 messenger ribonucleic acid (mRNA) levels in B lymphoblasts (BLCL) in BD patients compared to controls. We sought to determine if these same changes occur in non-Japanese populations and, if so, their relationship to altered basal intracellular Ca2+ ([Ca2+]B) in BLCL from BD patients.
Methods: Bipolar disorder patients and healthy subjects included 298 subjects of European Caucasian descent. The 5′-nuclease allelic discrimination TaqMan assay was used to detect selected single nucleotide polymorphisms (SNPs) in promoter, introns and 3′UTR regions, spanning the NDUFV2 gene. NDUFV2 mRNA levels and [Ca2+]B in BLCLs were determined.
Results: The A allele of the NDUFV2 SNP rs1156044 was significantly associated (Bonferroni-corrected) with BD (p = 0.013) but differed in allele (rs1156044 G allele) from that previously reported as associated with BD. There was a trend for elevated BLCL [Ca2+]B associated with SNP rs977581 in BD patients, but NDUFV2 mRNA levels in BLCLs did not differ between patients and controls, nor represented genotypes.
Conclusions: While genetic variants of NDUFV2 may increase risk for BD, the role of its altered expression and the link to intracellular Ca2+ abnormalities in BD remains equivocal.