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- Title
Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation.
- Authors
Zhang, Zhenxiao; Liu, Mingyang; He, Jianshuai; Zhang, Xiaotian; Chen, Yuehua; Li, Hui
- Abstract
<bold>Background: </bold>Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood.<bold>Methods: </bold>The subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included measuring the effects of the15910C > T mutation on tRNAThr levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both reactive oxygen species (ROS) and adenosine triphosphate (ATP).<bold>Results: </bold>We characterize mitochondrial genetic mutations in a three-generation Chinese family exhibiting signs of maternally inherited CHD. Of the 24 different family members in this pedigree we assessed, CHD was detected in 6, with variable severity and age of first appearance. When we sequenced the mitochondrial genomes of these individuals, we found a tRNAThr 15910C > T mutation of the Eastern Asian haplogroup M7b'c. This mutation is predicted to destabilize the strongly conserved (24C-10G) base-pairing, thereby disrupting tRNAThr functionality. When we performed Northern blotting, we detected we observed a 37.5% reduction in tRNAThr levels at baseline in cybrid cell lines bearing the 15910C > T mutation. When we conducted western blot analysis, we detected a ~ 24.96% decrease in mitochondrial translation rates in these same cells.<bold>Conclusions: </bold>In the present report, Together these findings suggest a possible link between this 15910C > T tRNAThr mutation and CHD, potentially offering new avenues for future disease intervention.
- Subjects
CORONARY disease; HEART diseases; TRANSFER RNA; WESTERN immunoblotting; MATHEMATICAL complexes; LEBER'S hereditary optic atrophy; GENETIC code; Y chromosome
- Publication
BMC Cardiovascular Disorders, 2019, Vol 19, Issue 1, p1
- ISSN
1471-2261
- Publication type
journal article
- DOI
10.1186/s12872-019-01284-4