Mitochondrial tRNA mutations in 2070 Chinese Han subjects with hypertension

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. The Sanger sequence analysis of 22 mitochondrial tRNA genes were performed in a cohort of 2070 Han Chinese hy...

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Published in:Mitochondrion 2016-09, Vol.30, p.208-221
Main Authors: Xue, Ling, Wang, Meng, Li, Haiying, Wang, Heng, Jiang, Feng, Hou, Lingling, Geng, Junwei, Lin, Zhi, Peng, Yanyan, Zhou, Hong, Yu, Han, Jiang, Pingping, Mo, Jun Qin, Guan, Min-Xin
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Asian Continental Ancestry Group
Case-Control Studies
China
DNA, Mitochondrial - chemistry
DNA, Mitochondrial - genetics
Electron Transport Chain Complex Proteins - analysis
Female
Gene Expression Profiling
Gene Frequency
Humans
Hypertension - pathology
Male
Middle Aged
Mutation
RNA, Transfer - genetics
Sequence Analysis, DNA
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Summary: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. 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 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. 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.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2016.08.008