Matrix Metalloproteinase-2 (MMP-2) Gene Polymorphism and Cardiovascular Comorbidity in Type 2 Diabetes Patients

Objective: Matrix metalloproteinases (MMPs) play an important role in pathogenesis of atherosclerosis and vascular disease. We hypothesized that MMP-2 might be a susceptibility gene for cardiovascular disease (CVD) in diabetes. The aim of this study was to evaluate the association between C(-1306)T functional polymorphism in the MMP-2 gene and risk of CVD in type 2 diabetes patients.

Methods: We examined 1090 patients with T2DM and 612 controls. All subjects were genotyped for the C(-1306)T polymorphism by polymerase chain reaction (PCR) and restriction analysis.

Results: A significant decrease of T allele frequency was observed in patients with CVD versus those with no CVD (OR 0.44, 95% CI 0.36-0.52, p<0.0001). In contrast, OR for CC genotype was 2.19 (1.79-2.68, p<0.0001), conferring 2-fold greater odds for CVD. When the distribution of C(-1306)T was compared in subgroups with different clinical phenotypes of CVD, patients with stroke had the lowest frequency of T allele (6% vs. 11%), compared to entire CVD+ group (p<0.05).

Conclusions: T2DM patients carrying the T allele of MMP-2 C(-1306)T polymorphism have a significantly reduced risk of CVD. The C(-1306)T polymorphism is associated with susceptibility to stroke in T2DM patients.