Polymorphism in the matrix metallopeptidase genes is associated with coronary artery disease risk with concomitant metabolic syndrome

Background: Metabolic syndrome (MS) and its components are the reasons of the development and progression of cardiovascular diseases. Nowadays, the association between coronary artery disease and MS remains ambiguous. The central role of matrix metallopeptidases (MMP) in the metabolism of connective tissue proteins, cell matrix remodeling, tissue repair and other complex biochemical processes has been shown, which implies their involvement in the pathogenesis of cardiovascular diseases. The aim of the study: To study the associations of polymorphic variants in the MMP genes with the risk of stable coronary artery disease with concomitant metabolic syndrome. Materials and methods: 170 patients with stable coronary artery disease concomitant with a visceral type of obesity in combination with two or more pathological conditions (elevated serum blood glucose level, elevated serum blood cholesterol level, hypertension) were included in the case group. Conditionally healthy volunteers (n=182) were recruited in the control group. Genotyping of five polymorphic sites in the four genes MMP1 (rs514921), MMP3 (rs6796620 and rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) was performed by real-time PCR. The serum blood level of MMP was measured by ELISA. Gene-gene interactions were analyzed using MDR v.3.0.2 software. Results: The frequency of heterozygous C/T genotype in the MMP3 gene (rs626750) was higher in the control group (37.90%) compared to the case group (23.20%), which indicates its protective effect on the risk of coronary artery disease with concomitant metabolic syndrome (OR=0.47, 95%CI 0.29-0.75). 2.6-fold increased risk of coronary artery disease with concomitant metabolic syndrome was demonstrated for carriers of the A/G genotype in the TIMP2 gene (rs2277698) according to the codominant inheritance model. We found no associations of polymorphic variants in the MMP1 (rs514921), MMP3 (rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) genes with the serum blood level of MMP, as well as their inhibitors. Four-loci model of gene-gene interactions (MMP9 (rs17576) – MMP3 (rs626750) – MMP1 (rs514921) – TIMP2 (rs2277698)) characterized by high sensitivity, specificity and risk effect to the coronary artery disease with concomitant metabolic syndrome development was discovered. Conclusion: This study revealed the association of polymorphic variants in the MMP genes and their inhibitors with the risk of coronary artery disease with concomitant metabolic syndrome. In addition, a four-locus model of intergenic interactions with high sensitivity and specificity was obtained.