Hypertension is a very common cardiovascular disorder, however, the molecular mechanism underlying this disease remains poorly understood. Recently, an increasing number of studies have demonstrated that mitochondrial (mt)DNA mutations serve important roles in the pathogenesis of hypertension. The current study reported the clinical and molecular characterization of a Chinese family with maternally inherited hypertension (the penetrance of hypertension was 71.4%). In addition, the entire mitochondrial transfer (mt-t)RNA genomes was amplified using a polymerase chain reaction (PCR) and identified through direct Sanger sequencing. Additionally, the mtDNA copy number in matrilineal relatives in this family was evaluated using quantitative PCR. The sequence analysis of the 22 mt-tRNA genes led to the identification of tRNAAla 5587T>C (thymine to cytosine) and tRNALeu(CUN) 12280A>G (adenine to guanine) mutations. Notably, the heteroplasmic 5587T>C mutation was located at the 3' end of tRNAAla (position 73), which is highly conserved from bacteria to human mitochondria. In addition, the 12280A>G mutation was revealed to occurs at the dihydrouridine loop of tRNALeu(CUN) (position 15) and may decrease the steady-state level of mt-tRNA. As a result, 5587T>C and 12280A>G mutations may lead to the failure of tRNAs metabolism and subsequently cause mitochondrial protein synthesis defects. Molecular analysis revealed that patients carrying the 5587T>C and 12280A>G mutations had a lower copy number of mtDNA compared with a control with hypertension, but without the mutations, suggesting that these mutations may cause mitochondrial dysfunctions that are responsible for hypertension. Therefore, mt-tRNAAla 5587T>C and tRNALeu(CUN) 12280A>G mutations may be involved in the pathogenesis of hypertension in this family.
Keywords: 12280A>G; 5587T>C; hypertension; mitochondrial; mutations; tRNA.