title: Mitochondrial tRNA mutations in 2070 Chinese Han subjects with hypertension.
abstract: 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 <1% of the controls; (2) evolutional conservation; (3) potential structural and functional alterations. We identified 47 (5 known and 42 novel/putative) hypertension-associated tRNA variants in 80 hypertensive subjects. These variants could have potential structural alterations and functional significance of tRNAs. By using lymphoblastoid cell lines derived from 6 probands carrying one of 6 represented variants (tRNA(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.
  
  
  
  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.
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xue
authors.affiliation: Institute of Genetics, Zhejiang University, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Hou
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Geng
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Institute of Genetics, Zhejiang University, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Institute of Genetics, Zhejiang University, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Genetics, Zhejiang University, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Rady Children's Hospital, University of California San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Jun Qin
authors.initials: JQ
authors.lastname: Mo
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Institute of Genetics, Zhejiang University, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joining Institute of Genetics and Genomic Medicine between Zhejiang University and University of Toronto, Hangzhou, Zhejiang, China. Electronic address: gminxin88@zju.edu.cn.
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012343:RNA, Transfer / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D012343:RNA, Transfer
keywords: Hypertension; Metabolism; Mitochondrial genetic defect; Pathophysiology; Translation; tRNA variants