Clinical and molecular characterization of a Han Chinese family with high penetrance of essential hypertension

Abstract

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 tRNALeu(CUN), was implied to cause a decrease in ND5 mRNA level as well as to alter tRNALeu(CUN) stability level. Moreover, the highly conserved 12,330A>G mutation, which disrupted the base pairing (6T-67A) in acceptor arm of tRNALeu(CUN), may result in the failure of tRNALeu(CUN) metabolism. Therefore, the combination of ND5 12,338T>C and tRNALeu(CUN) 12,330A>G mutations may contribute to the high penetrance of hypertension in this Chinese family.