Clinical and molecular characterization of a Han Chinese family with high penetrance of essential hypertension.
Mutations in mitochondrial DNA are associated with cardiovascular diseases. We reported here molecular characterization of a three-generation Han Chinese family with maternally transmitted hypertension. Most strikingly, this family exhibited a high penetrance of hypertension. Sequence analysis of mitochondrial genome showed the presence of 12,338T>C mutation and 12,330A>G mutation and distinct sets of polymorphisms belonging to the Asian haplogroup F2b. Interestingly, the well-known 12,338T>C mutation, which caused a change of methionine in the translational initiation codon of ND5, also localized in two nucleotides adjacent to the 3' end of tRNA(Leu(CUN)), was implied to cause a decrease in ND5 mRNA level as well as to alter tRNA(Leu(CUN)) stability level. Moreover, the highly conserved 12,330A>G mutation, which disrupted the base pairing (6T-67A) in acceptor arm of tRNA(Leu(CUN)), may result in the failure of tRNA(Leu(CUN)) metabolism. Therefore, the combination of ND5 12,338T>C and tRNA(Leu(CUN)) 12,330A>G mutations may contribute to the high penetrance of hypertension in this Chinese family.
Department of Geriatric Medicine, Shanghai East Hospital, Tongji University, Shanghai, PR China.
Lili
L
Teng
Jing
J
Zheng
Jianhang
J
Leng
Yu
Y
Ding
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D012356:RNA, Transfer, Leu / Q000235:genetics; D017385:Sequence Homology
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu