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 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.

Keywords::

• Hypertension
• mitochondrial DNA mutation
• tRNA metabolism
• Chinese family

Acknowledgments

We thank the patients for participating in this study.

Declaration of interest This work was supported by the grants from Nanjing Medical University (No. 2010NJMU011) and Ministry of Science and Technology from Shanghai Pudong new area (No. PKJ2010-Y08). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.