title: Novel mitochondrial DNA mutations associated with Chinese familial hypertrophic cardiomyopathy.
abstract: 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.
authors.affiliation: Institute of Material Medica and Department of Pharmaceutics, School of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wei
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Yu
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Li
authors.forename: Jian-Yan
authors.initials: JY
authors.lastname: Wen
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Zhao
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Liu
authors.forename: Yuan-Nan
authors.initials: YN
authors.lastname: Ke
authors.forename: William
authors.initials: W
authors.lastname: Campbell
authors.forename: Yi-Guan
authors.initials: YG
authors.lastname: Zhang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Liao
mesh_terms: 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
chemical_list: 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