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Mitochondrial tRNA mutations are associated with maternally inherited hypertension in two Han Chinese pedigrees

Authors

  • Qiaomeng Qiu,

    1. Departmnt of Emergency Medicine, the First Affiliated Hospital, of Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
    2. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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    • First three authors have equally contributed to this work.

  • Ronghua Li,

    1. Department of Genetics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China
    2. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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    • First three authors have equally contributed to this work.

  • Pingping Jiang,

    1. Department of Genetics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China
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    • First three authors have equally contributed to this work.

  • Ling Xue,

    1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Yang Lu,

    1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Yaman Song,

    1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Jungang Han,

    1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Zhongqiu Lu,

    1. Departmnt of Emergency Medicine, the First Affiliated Hospital, of Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
    2. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Shaoce Zhi,

    1. Departmnt of Emergency Medicine, the First Affiliated Hospital, of Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
    2. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
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  • Jun Qin Mo,

    1. Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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  • Min-Xin Guan

    Corresponding author
    1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, P. R. China
    2. Department of Genetics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China
    3. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
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  • Communicated by Ming Qi

Abstract

We report here the clinical, genetic, molecular, and biochemical evaluations in two Han Chinese families with maternally inherited hypertension. Fourteen of 20 adult matrilineal relatives of these families exhibited a wide range of severity in hypertension, while none of offspring of affected fathers had hypertension. The age-at-onset of hypertension in matrilineal relatives varied from 37 years to 83 years, with an average of 55 and 66 years, respectively. Mutational analysis of their mitochondrial genomes identified the m.4353T>C mutation in the tRNA, in conjunction with the known m.593C>T mutation in the tRNAPhe and m.5553C>T mutation in the tRNATrp. Northern analysis revealed that m.4353T>C, m.593C>T and m.5553C>T mutations caused ∼66%, 65%, and 12% reductions in the steady-state level of tRNAGln, tRNAPhe and tRNATrp, respectively. An in vivo protein labeling analysis showed ∼35% reduction in the rate of mitochondrial translation in cells carrying these tRNA mutations. Impaired mitochondrial translation is apparently a primary contributor to the reduced rates of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or N,N,N′,N′-tetramethyl-p-phenylenediamine/ascorbate-promoted respiration and the increasing level of reactive oxygen species in the cells carrying these mtDNA mutations. These data demonstrate that mitochondrial dysfunction caused by mitochondrial tRNA mutations is associated with essential hypertension in these families. Hum Mutat 33:1285–1293, 2012. © 2012 Wiley Periodicals, Inc.

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