title: Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder.
abstract: Linkage of bipolar disorder with 18p11 has been replicated by several investigators. A nuclear-encoded mitochondrial complex I subunit gene, NDUFV2, is one of the candidate genes in this locus, since the possible pathophysiological significance of mitochondrial dysfunction in bipolar disorder has been suggested. The objective of our study was to clarify the association between the NDUFV2 gene and bipolar disorder. We performed the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) for NDUFV2 mRNA expression in lymphoblastoid cell lines derived from patients with bipolar disorder and healthy controls. We also screened novel polymorphisms using denaturing high performance liquid chromatography (D-HPLC) and PCR-direct sequencing method. Detected five single nucleotide polymorphisms (SNPs) were genotyped. A decrease of the expression level of NDUFV2 gene was found in patients with bipolar I disorder compared with controls (P = 0.006). We also found that the haplotype frequencies of the four polymorphisms in the upstream region of NDUFV2 were significantly different between bipolar disorders and controls (P = 0.0001). Our findings suggest that polymorphisms of the NDUFV2 gene may be one of the genetic risk factors for bipolar disorder.
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Saitama, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Washizuka
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kakiuchi
authors.forename: Kanako
authors.initials: K
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Osamu
authors.initials: O
authors.lastname: Tajima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nanko
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004272:DNA, Mitochondrial; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger