Matrix metalloproteinase-3 and Matrix metalloproteinase-9 genetic variation in a cohort of patients with coronary artery disease

Abstract

Matrix metalloproteinases (MMPs) disequilibrium in atherosclerosis plaques is influenced by genetic variations. MMP-3 and MMP-9 levels may be affected by existent single nucleotide polymorphisms: the-1171 5A/6A and the - 1562 C/T respectively existent at their promoter site. We aim in our study to prospectively investigate the impact of these polymorphisms on a cohort of patients with a history of coronary artery disease (CAD) One hundred sixty-eight CAD patients were prospectively followed for 5 years. These patients were genotyped by PCR-RFLP for the MMP-9 -1562 C/T and the MMP-3-1171 5A/6A polymorphism. Their levels were measured by ELISA in Sandwich test. Forty-five fatal and non-fatal cardiovascular event occurred during the cohort period. Genotypes of both polymorphisms were in Hardy-Weinberg equilibrium. The MMP-3 5A/6A polymorphism was related to the disease on the contrary of the MMP-9. Patients carrying the 5A allele had a higher level of MMP-3 level and those who carried the 6A allele had lower level ( P = 0.04). MMP-9 circulating level was not related to the −1562 C/T polymorphism. Individuals with the 6A allele presented a higher prevalence of the disease than the carriers of the 5A allele even after adjustment for probable confounding factors (age, gender, hypertension, diabetes, CRP, eGFR, and treatment) (HR = 4.41, P :0.02 (95%CI: 1.16–16.69). Kaplan–Meier survival test revealed that individuals having the 6A allele had a lower survival rate than those with the 5A allele ( P = 0.01). The 6A allele is independently implicated in the occurrence of the fatal and non-fatal cardiovascular. Its existence is related to the lower survival rate.