Abstract
The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of coronary artery calcification (CAC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with CAC. One hundred and fifty-five cases with CAC and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR–RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS (fasting blood sugar), urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with CAC when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to CAC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in CAC cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code Availability
N/A.
Abbreviations
- BMI:
-
Body mass index
- CAC:
-
Coronary artery calcification
- DBP:
-
Diastolic blood pressure
- SBP:
-
Systolic blood pressure
- SNP:
-
Single-nucleotide polymorphism
- HDL:
-
High-density lipoprotein
- LDL:
-
Low-density lipoprotein
- DFU:
-
Diabetic foot ulcers
- ECM:
-
Extracellular matrix
- FBS:
-
Fasting blood sugar
- HWE:
-
Hardy–Weinberg equilibrium
- T2DM:
-
Type 2 diabetes mellitus
- Tg:
-
Triglyceride
- WT:
-
Wild type
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Acknowledgements
This work was performed in partial fulfillment of the requirements for the biochemistry MSc thesis of Saeed Elahirad, in the School of Medicine, Kermanshah University of Medical Sciences Kermanshah, Iran. The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant Number 95294) for financial support.
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This work was supported by the Research Council of Kermanshah University of Medical Sciences (Grant No.: 95294).
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by SE, DEAK, and AK. The first draft of the manuscript was written by AK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Elahirad, S., Elieh Ali Komi, D., Kiani, A. et al. Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Polymorphisms, Their Serum Levels, and Activities with Coronary Artery Calcification (CAC) in an Iranian Population. Cardiovasc Toxicol 22, 118–129 (2022). https://doi.org/10.1007/s12012-021-09707-5
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DOI: https://doi.org/10.1007/s12012-021-09707-5