Polymorphisms of MMP-3 and TIMP-4 Genes Affect Angiographic Coronary Plaque Progression in Non-diabetic and Type 2 Diabetic Patients

Background: This study examined whether genetic variants of matrix metallopeptidases (MMPs) and their tissue inhibitors (TIMPs) were associated with angiographic coronary plaque progression (PP) in type 2 diabetic and non-diabetic patients.

Methods: Four hundred and ninety-nine patients were grouped, who underwent coronary angiography and received repeat examinations after 1-y follow-up. Twelve functional polymorphisms of MMPs and TIMPs were characterized.

Results: Genotype distribution and allele frequency of -1612 5A/6A MMP-3 and 3'UTR C/T TIMP-4 differed between patients with PP and those without in both diabetic and non-diabetic groups after Bonferroni's correction (all P<0.0041667, except for allele frequency of MMP-3 [P=0.007] and genotype/allele frequency of TIMP-4 [P=0.04 and P=0.016, respectively] in diabetes). MMP-3 and TIMP-4 polymorphisms were associated with changes in percent diameter stenosis and minimal lumen diameter in diabetic patients, and changes in cumulative coronary obstruction in both diabetic and non-diabetic patients (all P<0.05). Multivariable regression analysis revealed that hypertension, low HDL-C and genotypes of MMP-3 and TIMP-4 were independent determinants of PP in the whole patients, with these 2 genetic factors being associated with PP in diabetic and non-diabetic subgroups.

Conclusion: This study demonstrated that MMP-3 and TIMP-4 polymorphisms affect angiographic coronary PP in type 2 diabetic and non-diabetic patients.