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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

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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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Data Availability

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.

Funding

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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Correspondence to Nahid Salehi.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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This study was approved by the ethics committee of Kermanshah Medical University (EC. 95294). All patients signed a consent form.

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Informed consent was obtained from all individual participants included in the study.

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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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