Novel mitochondrial DNA mutations associated with Chinese familial hypertrophic cardiomyopathy.
1. Hypertrophic cardiomyopathy (HCM) is a genetic disorder that has a complex set of symptoms and potentially devastating consequences. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations are responsible for the development of HCM, but the mtDNA mutations appear to differ considerably among different populations and regions. 2. In the present study, three families with HCM were found and investigated: one in Shandong province and two in the Chongqing region of China. The entire mtDNA genome from the 18 affected and 66 unaffected family members was sequenced directly and the mtDNA mutations were determined. 3. The frequency of haplogroup M10 was significantly higher in family members with HCM (HCM group) than in unaffected family members (normal group). Three mtDNA mutations were found with a significantly higher frequency in affected individuals than in unaffected family individuals, namely G7697A in the cytochrome c oxidase subunit II gene (P < 0.0001; odds ratio (OR) 227.5; 95% confidence interval (CI) 23.6–2194.8) and T12477C (P = 0.0037; OR 5.6; 95% CI 1.8–17.6) and G13135A in the NADH dehydrogenase 5 gene (P < 0.0001; OR 26.0; 95% CI 6.9–98.3), suggesting that these mutations are probably associated with susceptibility to HCM. In addition, mitochondrial Complex I activity was markedly decreased in the HCM group, suggesting that these mutations most likely affect mitochondrial respiratory function. 4. In conclusion, the results of the present study imply that mtDNA mutations G7697A, T12477C and G13135A are genetic factors that indicate a susceptibility to HCM and that could be used for the large-scale screening of genetic markers as well as the early diagnosis of HCM.
Wei
Yan-Ling
YL
Institute of Material Medica and Department of Pharmaceutics, School of Pharmacy, Third Military Medical University, Chongqing, China.
Yu
Chang-An
CA
Yang
Peng
P
Li
Ai-Li
AL
Wen
Jian-Yan
JY
Zhao
Shu-Min
SM
Liu
Hong-Xing
HX
Ke
Yuan-Nan
YN
Campbell
William
W
Zhang
Yi-Guan
YG
Li
Xiao-Hui
XH
Liao
Wen-Qiang
WQ
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography; D055815:Young Adult
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I