The Mitochondrial tRNALeu(UUR) A3302G Mutation may be Associated With Insulin Resistance in Woman With Polycystic Ovary Syndrome.
The aim of this study was to investigate the role of mitochondrial DNA (mtDNA) mutations in polycystic ovary syndrome (PCOS) with insulin resistance (IR), and to explore the possible maternally effects on PCOS. We performed clinical, genetic, and molecular characterization of a Han Chinese family with maternally inherited IR, and we further investigated the possible relationship between mitochondrial genetic background, copy number, and IR. Most strikingly, members from the first and second generation of this family exhibited the type 2 diabetes mellitus (T2DM) with IR, while the member in the third generation of this family manifested the PCOS. Sequence analysis of the complete mitochondrial genome showed the presence of a homoplasmic A3302G in the acceptor arm of transfer RNA(Leu(UUR)) (tRNA(Leu(UUR))) gene. This mutation disrupted the highly conserved base pairing (2T-71A) and resulted a failure in mt-tRNA metabolism. Analysis of the mitochondrial copy number showed that the patients with PCOS and IR had lower copy number than the health controls, suggesting that mitochondrial dysfunction may be involved in the pathogenesis of IR. Taken together, the A3302G mutation was a pathogenic mutation associated with IR in this Chinese family.
Central laboratory, Hangzhou First People's Hospital, Hangzhou, China Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, China dingyu.zj@gmail.com.
Yu
Y
Ding
Central laboratory, Hangzhou First People's Hospital, Hangzhou, China Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, China.
Guangchao
G
Zhuo
Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, China Department of Gynecology and Obstetrics, Hangzhou First People's Hospital, Hangzhou, China.
Caijuan
C
Zhang
D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D012356:RNA, Transfer, Leu / Q000235:genetics* / Q000378:metabolism
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu
A3302G mutation; IR; PCOS; maternally inherited; mitochondrial tRNALeu(UUR)