TY - JOUR
T1 - Matrix metalloproteinase-3 (MMP-3) polymorphisms are associated with prolonged ECG-derived QTc interval
T2 - A cross-sectional study of the Australian rural population
AU - Lu, Yaxin
AU - Ussher, Nathan
AU - Zhou, Yuling
AU - Jelinek, Herbert
AU - Hambly, Brett
AU - Li, Amy
AU - McLachlan, Craig S.
N1 - Publisher Copyright:
© 2021 by the authors.
PY - 2021/7/23
Y1 - 2021/7/23
N2 - 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.
AB - 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.
KW - ECG
KW - Matrix metalloproteinases
KW - MMP-3
KW - Rural populations
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U2 - 10.3390/jpm11080705
DO - 10.3390/jpm11080705
M3 - Article
C2 - 34442348
AN - SCOPUS:85111426768
SN - 2075-4426
VL - 11
SP - 1
EP - 9
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
IS - 8
M1 - 705
ER -