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Background: Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood. Objective: To investigate the mitochondrial tRNA mutation associated with CHD. Methods: We are conducting ongoing systematic screening efforts assessing mtDNA mutations among Chinese CHD patients. And we followed up on its biological significance in cybrid cell lines bearing this mutation, measuring the effects of this15910C>T mutation on tRNAThr levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both ROS and ATP. Results:In the present report, 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 cells 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. Conclusions: Together these findings suggest a possible link between this 15910C>T tRNAThr mutation and CHD, potentially offering new avenues for future disease intervention.
Keywords
Coronary heart disease (CHD), mitochondrial tRNA, mutation, Chinese
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CURRENT STATUS: Published
View the published article at BMC Cardiovascular Disorders.
Version 1
Posted 30 Jul, 2019
No community comments so far
Reviewer #4 agreed
On 28 Aug, 2019
Reviewer #3 agreed
On 26 Aug, 2019
Review #1 received
Received 22 Aug, 2019
Review #2 received
Received 20 Aug, 2019
Reviewer #2 agreed
On 06 Aug, 2019
Reviewer #1 agreed
On 05 Aug, 2019
Reviewers invited
Invitations sent on 04 Aug, 2019
Submission checks complete
On 25 Jul, 2019
Editor invited
On 25 Jul, 2019
Editor assigned
On 15 Jul, 2019
First submitted
On 11 Jul, 2019
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Subject Areas
Cardiac & Cardiovascular Systems
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A new preprint design is coming!
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See the published version of this preprint at BMC Cardiovascular Disorders.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cardiovascular Disorders.
Version 1
Posted 30 Jul, 2019
No community comments so far
Reviewer #4 agreed
On 28 Aug, 2019
Reviewer #3 agreed
On 26 Aug, 2019
Review #1 received
Received 22 Aug, 2019
Review #2 received
Received 20 Aug, 2019
Reviewer #2 agreed
On 06 Aug, 2019
Reviewer #1 agreed
On 05 Aug, 2019
Reviewers invited
Invitations sent on 04 Aug, 2019
Submission checks complete
On 25 Jul, 2019
Editor invited
On 25 Jul, 2019
Editor assigned
On 15 Jul, 2019
First submitted
On 11 Jul, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cardiac & Cardiovascular Systems
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cardiovascular Disorders.
Background: Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood. Objective: To investigate the mitochondrial tRNA mutation associated with CHD. Methods: We are conducting ongoing systematic screening efforts assessing mtDNA mutations among Chinese CHD patients. And we followed up on its biological significance in cybrid cell lines bearing this mutation, measuring the effects of this15910C>T mutation on tRNAThr levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both ROS and ATP. Results:In the present report, 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 cells 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. Conclusions: Together these findings suggest a possible link between this 15910C>T tRNAThr mutation and CHD, potentially offering new avenues for future disease intervention.
Figure 1
Figure 2
Figure 3
Figure 4
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