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

• DOI: 10.1007/s12012-021-09707-5
• Publication Date: 2021-11-03T09:03:12Z
• Authors: Saeed Elahirad; Daniel Elieh Ali ...; Amir Kiani; Ehsan Mohammadi-N...; Asad Vaisi‑Raygani; Hadi Mozafari; Fariborz Bahrehmand; Mohammadreza Saidi; Vahid Toupchi-Kho...; Nahid Salehi
• Keywords: Male; 0303 health sciences; Enzyme-Linked Immunosorbent Assay; Coronary Artery Disease; Iran; Middle Aged; Lipids; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Phenotype; Gene Frequency; Matrix Metalloproteinase 9; Predictive Value of Tests; Case-Control Studies; Humans; Matrix Metalloproteinase 2; Female; Genetic Predisposition to Disease; Biomarkers; Genetic Association Studies; Aged

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.