Further support for association of the mitochondrial complex I subunit gene NDUFV2 with bipolar disorder.
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 Ca(2+) ([Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](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 Ca(2+) abnormalities in BD remains equivocal.
Xu
Chun
C
Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Li
Peter P
PP
Kennedy
James L
JL
Green
Marty
M
Hughes
Bronwen
B
Cooke
Robert G
RG
Parikh
Sagar V
SV
Warsh
Jerry J
JJ
D001714:Bipolar Disorder / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D009245:NADH Dehydrogenase; C492562:NDUFV2 protein, human