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Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population

Matrix metalloproteinases (MMPs) are enzymes that are integral in extracellular matrix (ECM) remodeling. In age or disease, ECM may become dysregulated and contribute to fibrosis, which impairs cardiac electrical conduction. Two alleles regulate matrix metalloproteinase-3 (MMP-3) activity: one with...

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Autores principales: Lu, Yaxin, Ussher, Nathan, Zhou, Yuling, Jelinek, Herbert, Hambly, Brett, Li, Amy, McLachlan, Craig S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399546/
https://www.ncbi.nlm.nih.gov/pubmed/34442348
http://dx.doi.org/10.3390/jpm11080705
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author Lu, Yaxin
Ussher, Nathan
Zhou, Yuling
Jelinek, Herbert
Hambly, Brett
Li, Amy
McLachlan, Craig S.
author_facet Lu, Yaxin
Ussher, Nathan
Zhou, Yuling
Jelinek, Herbert
Hambly, Brett
Li, Amy
McLachlan, Craig S.
author_sort Lu, Yaxin
collection PubMed
description Matrix metalloproteinases (MMPs) are enzymes that are integral in extracellular matrix (ECM) remodeling. In age or disease, ECM may become dysregulated and contribute to fibrosis, which impairs cardiac electrical conduction. Two alleles regulate matrix metalloproteinase-3 (MMP-3) activity: one with five adenosine bases (5A; associated with higher MMP-3 activity and decreased fibrosis) and another with six adenosine bases (6A; associated with lower MMP-3 activity and increased fibrosis). Here, we determined whether ECG-derived QTc and related parameters are associated with the MMP-3 5A/6A genotype in a cross-section of the Australian rural population. A retrospective cross-sectional population was obtained from the Charles Sturt University Diabetes Screening Research Initiative. Genotype and resting 12-lead ECG parameters of 295 participants were analyzed. Amongst these participants, 85 individuals carried the 5A/5A genotype, 141 individuals carried the 5A/6A genotype, and 65 individuals carried the 6A/6A genotype. Compared to 5A/5A genotype carriers, 5A/6A genotype carriers had a significantly longer QTc duration by 9.50 ms (95% CI: 3.48–15.52, p = 0.002), whilst 6A/6A genotype carriers had an even longer QTc duration by 12.19 ms (95% CI: 5.04–19.34, p = 0.001). We found an association between MMP-3 5A/6A polymorphisms and QTc, independent of adjustments for age, gender, alcohol consumption, smoking status, body mass index and blood pressure.
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spelling pubmed-83995462021-08-29 Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population Lu, Yaxin Ussher, Nathan Zhou, Yuling Jelinek, Herbert Hambly, Brett Li, Amy McLachlan, Craig S. J Pers Med Article Matrix metalloproteinases (MMPs) are enzymes that are integral in extracellular matrix (ECM) remodeling. In age or disease, ECM may become dysregulated and contribute to fibrosis, which impairs cardiac electrical conduction. Two alleles regulate matrix metalloproteinase-3 (MMP-3) activity: one with five adenosine bases (5A; associated with higher MMP-3 activity and decreased fibrosis) and another with six adenosine bases (6A; associated with lower MMP-3 activity and increased fibrosis). Here, we determined whether ECG-derived QTc and related parameters are associated with the MMP-3 5A/6A genotype in a cross-section of the Australian rural population. A retrospective cross-sectional population was obtained from the Charles Sturt University Diabetes Screening Research Initiative. Genotype and resting 12-lead ECG parameters of 295 participants were analyzed. Amongst these participants, 85 individuals carried the 5A/5A genotype, 141 individuals carried the 5A/6A genotype, and 65 individuals carried the 6A/6A genotype. Compared to 5A/5A genotype carriers, 5A/6A genotype carriers had a significantly longer QTc duration by 9.50 ms (95% CI: 3.48–15.52, p = 0.002), whilst 6A/6A genotype carriers had an even longer QTc duration by 12.19 ms (95% CI: 5.04–19.34, p = 0.001). We found an association between MMP-3 5A/6A polymorphisms and QTc, independent of adjustments for age, gender, alcohol consumption, smoking status, body mass index and blood pressure. MDPI 2021-07-23 /pmc/articles/PMC8399546/ /pubmed/34442348 http://dx.doi.org/10.3390/jpm11080705 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Yaxin
Ussher, Nathan
Zhou, Yuling
Jelinek, Herbert
Hambly, Brett
Li, Amy
McLachlan, Craig S.
Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title_full Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title_fullStr Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title_full_unstemmed Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title_short Matrix Metalloproteinase-3 (MMP-3) Polymorphisms Are Associated with Prolonged ECG-Derived QTc Interval: A Cross-Sectional Study of the Australian Rural Population
title_sort matrix metalloproteinase-3 (mmp-3) polymorphisms are associated with prolonged ecg-derived qtc interval: a cross-sectional study of the australian rural population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399546/
https://www.ncbi.nlm.nih.gov/pubmed/34442348
http://dx.doi.org/10.3390/jpm11080705
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