Mitochondrial tRNA mutations in 2070 Chinese Han subjects with hypertension

Abstract Background Mitochondria have the profound impact on vascular function in both health and disease. However, mitochondrial genetic determinants for the development of hypertension remain poorly explored. Methods and results The Sanger sequence analysis of 22 mitochondrial tRNA genes were performed in a cohort of 2070 Han Chinese hypertensive and 512 control subjects. This analysis identified 165 variants among 22 tRNA genes. These variants were evaluated for the pathogenicity using the following criteria: (1) present in Ala 5655T > C, tRNA Gly 10003T > C, tRNA Leu(UUR) 3253T > C, tRNA Asp 7551A > G, tRNA Glu 14692A > G, tRNA Thr 15909A > G) and 6 control subjects lacking these variants, we showed marked reductions in the steady-state level of corresponding 5 tRNAs, but not tRNA Thr , in mutant cell lines, compared with control cells lines. The various decreases in the activities of complexes I, III and IV were observed in mutant cells carrying one of five tRNA variants, except tRNA Thr 15909A > G variant. The deficient respirations were responsible for the decrease in the mitochondrial ATP production and increasing production of reactive oxygen species in mutant cell lines carrying one of five tRNA variants. Conclusion Mitochondrial tRNA variants are the important causes of hypertension, accounting for 3.9% cases of 2070 Han Chinese hypertensive subjects. Our findings may provide new insights into the pathophysiology of hypertension that were manifested by mitochondrial dysfunction.