Influence of gelatinase B polymorphic variants and its serum levels in atherosclerosis

Atherosclerosis, the underlying pathology of cardiovascular disease, is a common, multifactorial disorder with both genetic and environmental components as risk factors. Gelatinase B, also known as MMP-9, is one of the matrix metalloproteinases that is highly expressed in the disruption-prone regions of atherosclerotic plaques. It has been hypothesized that a genetic variation affecting the expression or activity of MMP-9 influences the susceptibility and progression of atherosclerosis. The present study aims to ascertain the polymorphic variants of the MMP-9 gene promoter and its serum levels, which contribute to interindividual differences in susceptibility to atherosclerosis. The study population consisted of 200 individuals who include 100 cases with angiographically recorded coronary artery disease (CAD) and 100 age- and sex-matched healthy controls. Serum levels of MMP-9 were determined in these subjects using an enzyme-linked immunosorbent assay, and polymorphic genotypes of MMP-9 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay.

The MMP-9 levels among subjects with the TT genotype for controls (12.21±2.39) and CAD (22.86±2.45) were significantly higher than that of CC genotype (controls 10.37±1.42 and CAD 16.44±7.99), and the values were intermediate for the CT genotype (control 11.21±2.01 and CAD 18.80±3.17) and found to be significant at p<0.01. Genotypic analysis of -1562C/T polymorphism among patients and controls showed higher T allele frequencies in the patient group (0.36) than in the controls (0.29).

It has been observed that increased MMP-9 expression in T allele carriers may contribute to the severity of coronary atherosclerosis. These findings not only are relevant to the understanding of the pathogenesis of atherosclerosis but also may provide a novel target for future development of predictive, preventive, and therapeutic measures.