Gene polymorphisms and antigen levels of matrix metalloproteinase-1 in type 2 diabetes mellitus coexisting with coronary heart disease.

BACKGROUND AND AIM

Diabetes mellitus is a major risk factor for coronary heart disease (CHD). Matrix metalloproteinases (MMPs) can play a pivotal role in the remodelling of extracellular matrix associated with the development of atherosclerosis. Therefore, the aim of the study was to compare the distribution of genotypes and frequency of alleles of two polymorphisms of the MMP-1 gene promoter, an A/G substitution and a 1G/2G insertion, in correlation with antigen levels of matrix metalloproteinase-1 (MMP-1) in type 2 diabetic patients with or without CHD as well as individuals with normal glucose level without CHD.

METHODS

Genotypes of 115 patients with type 2 diabetes mellitus (T2DM) and a subpopulation of 66 patients with coexisting CHD as well as 120 non-diabetic control subjects were determined by PCR-based restriction fragment length polymorphism (PCR-RFLP).

RESULTS

We demonstrated that antigen levels of MMP-1 in the serum of diabetic patients were significantly higher than those of individuals with normal glucose metabolism (p <0.05). Elevated levels of MMP-1 positively correlated with CHD occurrence in T2DM patients (p <0.01). The distribution of genotypes revealed higher frequency of the 2G/2G polymorphism variant in diabetic patients with CHD [OR 5.76, 95% CI (1.24; 26.87)], thus suggesting its strong association with high level of MMP-1. In T2DM patients with coexisting CHD, a higher frequency of the 2G allele of 1G/2G [OR 1.74, CI 95% (1.01; 2.99)] and the G allele of A/G polymorphism [OR 2.15, 95% CI (1.22; 3.80)] was also found.

CONCLUSION

Our results suggest that type 2 diabetes mellitus is linked with elevated blood level of MMP-1, and polymorphisms of the promoter region of its gene might be associated with CHD.