Expression of mitochondria-related genes in lymphoblastoid cells from patients with bipolar disorder.
OBJECTIVE
Several studies have suggested mitochondrial abnormality in bipolar disorder. We reported the association of mitochondrial complex I subunit gene, NDUFV2 at 18p11, with bipolar disorder. A decrease in the mRNA expression of this gene was found in patients with bipolar disorder compared with controls. However, it was unclear whether only the NDUFV2 gene exhibited the decreased expression level in bipolar disorder. The aim of this study was to clarify the association of other nuclear-encoded complex I subunit genes and mitochondria-related genes with bipolar disorder.


METHODS
We quantified the mRNA expression level of five nuclear-encoded mitochondrial complex I subunit genes located at the chromosomal regions linked with bipolar disorder other than NDUFV2, three complex IV subunit genes, and four mitochondrial transcription-related genes using a real-time quantitative reverse transcription polymerase chain reaction method in the lymphoblastoid cell lines from 21 patients with bipolar disorder and 11 controls.


RESULTS
Decreased mRNA expression in patients with bipolar I disorder compared with control subjects was found in most of the complex I subunit genes. In addition, decreased expression levels of these genes correlated with that of NDUFV2. No statistically significant alterations of mRNA expression levels were found between bipolar patients and controls among two of three complex IV subunit genes and all transcription-related genes.


CONCLUSIONS
Our study suggests that the decreased expression of NDUFV2 has a considerable effect on other subunit genes in the mitochondrial respiratory chain and presents further evidence of the biological significance of NDUFV2 in bipolar disorder.
Washizuka
Shinsuke
S
Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, Saitama, Japan.
Kakiuchi
Chihiro
C
Mori
Kanako
K
Tajima
Osamu
O
Akiyama
Tsuyoshi
T
Kato
Tadafumi
T
D001714:Bipolar Disorder / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D005260:Female; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009245:NADH Dehydrogenase; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C492562:NDUFV2 protein, human