The Mitochondrial tRNAAla T5655C Mutation May Modulate the Phenotypic Expression of tRNAMet and tRNAGln A4401G Mutation in a Han Chinese Family With Essential Hypertension.

Mutations in mitochondrial DNA are associated with the pathogenesis of essential hypertension. We report here the clinical, genetic, and molecular characterization of a three-generation Han Chinese family with essential hypertension. Most strikingly, this family exhibited a high penetrance of essential hypertension. Sequence analysis of the mitochondrial genome showed the presence of a homoplasmic T5655C mutation in tRNAAla, together with the A4401G mutation in the adjacent region between tRNAMet and tRNAGln. Notably, the T5655C mutation was localized at the acceptor arm of tRNAAla, disrupted the high conserved base-pairing (1A-72T), and may impair the tRNA function. Moreover, the A4401G mutation was reported to decrease the steady-state level of tRNAMet and tRNAGln, and consequently caused the mitochondrial dysfunction responsible for hypertension. Taken together, the combination of T5655C and A4401G mutations in mitochondrial tRNA genes may account for the high penetrance and expressivity of hypertension in this Chinese family. Thus, our findings may provide new insight into the pathogenesis of this disorder.