Mitochondrial Genetics and Human Systemic Hypertension

Marian, Ali J.

doi:10.1161/circresaha.111.242768

Cited by 25 publications

(19 citation statements)

References 24 publications

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“…16) Recently, increasing evidence has shown that mitochondrial dysfunction caused by mtDNA mutations plays an important role in the development of EH, and mitochondrial dysfunction will increase the production of reactive oxygen species (ROS), which will lead to oxidative stress, loss of nitric oxide signaling and endothelial barrier function, and infiltration of leukocytes into the vascular wall, and thus, contribute to high blood pressure. 17,18) Today, approximately 200 pathogenic mutations had been mapped to mttRNA genes (http://www.mitomap.org/MITOMAP), 19) emphasizing the importance of mt-tRNAs for mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

The Mitochondrial tRNAAla T5655C Mutation May Modulate the Phenotypic Expression of tRNAMet and tRNAGln A4401G Mutation in a Han Chinese Family With Essential Hypertension

Chen

Huang

et al. 2017

Int. Heart J.

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SummaryMutations in mitochondrial DNA are associated with the pathogenesis of essential hypertension. We report here the clinical, genetic, and molecular characterization of a three-generation Han Chinese family with essential hypertension. Most strikingly, this family exhibited a high penetrance of essential hypertension. Sequence analysis of the mitochondrial genome showed the presence of a homoplasmic T5655C mutation in tRNA Ala , together with the A4401G mutation in the adjacent region between tRNA Met and tRNA Gln. Notably, the T5655C mutation was localized at the acceptor arm of tRNA Ala , disrupted the high conserved base-pairing (1A-72T), and may impair the tRNA function. Moreover, the A4401G mutation was reported to decrease the steady-state level of tRNA Met and tRNA Gln, and consequently caused the mitochondrial dysfunction responsible for hypertension. Taken together, the combination of T5655C and A4401G mutations in mitochondrial tRNA genes may account for the high penetrance and expressivity of hypertension in this Chinese family. Thus, our findings may provide new insight into the pathogenesis of this disorder. (Int Heart J 2017; 58: 95-99)

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Section: Discussionmentioning

confidence: 99%

The Mitochondrial tRNAAla T5655C Mutation May Modulate the Phenotypic Expression of tRNAMet and tRNAGln A4401G Mutation in a Han Chinese Family With Essential Hypertension

Chen

Huang

et al. 2017

Int. Heart J.

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“…Recently, several mtDNA point mutations have been identified to be associated with cardiovascular disease including the essential hypertension [4][5][6][7]. Investigators have provided further evidence of a maternal effect on hypertension status and systolic blood pressure [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of mitochondrial tRNALys mutation on the clinical and biochemical characteristics of Chinese essential hypertensive subjects

Xiao

Zhang

et al. 2014

Biochemical and Biophysical Research Communications

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“…Hypertension can be caused by single‐gene or multifactorial conditions, resulting from interactions between the environment and inherited risk factors [Lifton et al, 2001]. Of hereditary factors, maternal transmissions of hypertension have been implicated in some pedigrees, suggesting that the mutation(s) in mitochondrial DNA (mtDNA) is responsible for the phenotype [Marian, 2011; Ruiz‐Pesini et al, 2007; Wilson et al, 2004; Watson et al, 2001]. Several mtDNA mutations including m.4435A>G mutation in the tRNA Met (MIM# 590065) and m.4263A>G mutation in the tRNA Ile (MIM# 590045) as well as m.4401A>G mutation in the junction of tRNA Gln (MIM# 590030) and tRNA Met genes have been associated with essential hypertension in some Chinese families [Li et al, 1999; Liu et al, 2009; Lu et al, 2011; Wang et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

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

Qiu

Jiang

et al. 2012

Hum. Mutat.

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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 tRNA(Phe) and m.5553C>T mutation in the tRNA(Trp). 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 tRNA(Gln), tRNA(Phe) and tRNA(Trp), 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.

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Mitochondrial Genetics and Human Systemic Hypertension

Cited by 25 publications

References 24 publications

The Mitochondrial tRNA<sup>Ala</sup> T5655C Mutation May Modulate the Phenotypic Expression of tRNA<sup>Met</sup> and tRNA<sup>Gln</sup> A4401G Mutation in a Han Chinese Family With Essential Hypertension

The Mitochondrial tRNA<sup>Ala</sup> T5655C Mutation May Modulate the Phenotypic Expression of tRNA<sup>Met</sup> and tRNA<sup>Gln</sup> A4401G Mutation in a Han Chinese Family With Essential Hypertension

Effect of mitochondrial tRNALys mutation on the clinical and biochemical characteristics of Chinese essential hypertensive subjects

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

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