High serum level of matrix metalloproteinase 9 and promoter polymorphism - 1562 C:T as a new risk factor for metabolic syndrome

Abstract

The altered matrix metalloproteinases (MMPs) have been suggested in the pathophysiology of metabolic syndrome (MetS). Genetic variants in the promoter region of MMP1 and MMP9 genes may modulate an individual's susceptibility to MetS. The aim of this study was to determine the frequency of MMP1 -519 A:G and MMP9 -1562 C:T polymorphisms and the correlation with serum levels of MMP1 and MMP9 in MetS susceptibility. On the basis of anthropometric profile and laboratory investigations, 180 confirmed MetS patients and 190 unrelated healthy controls of similar ethnicity were genotyped for MMP1 -519 A:G and MMP9-1562 C:T polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. In addition, serum levels of MMP1 and MMP9 were quantified by ELISA. We found that the serum level of MMP9 was significantly higher in MetS patients. Variant genotype TT of MMP9 -1562 demonstrated increased risk (odds ratio [OR]=3.70, p=0.015) of MetS. Similarly, variant allele T (OR=1.77, p=0.002) and combined genotype CT+TT (OR=1.81, p=0.057) also showed a significantly higher risk. The CT and TT genotypes of MMP9 -1562 polymorphism contributed to high serum levels of MMP9 in MetS patients. However, no such association was observed with the MMP1 serum level and -519 A:G polymorphism. Our results suggest that a higher serum level of MMP9 in the presence of MMP9 polymorphism -1562 C:T might be a risk factor for the development of MetS. The MMP9 enzyme activity might be a significant indicator in the screening of MetS patients.

FIG. 1.

(A) Serum level of MMP9 and MMP1 genes in MetS and control. Data represented as mean±SD. (B) Association between MMP1 −519 A:G polymorphism and the serum level in MetS and control. (C) Association between MMP9 −1562 C:T polymorphism and the serum level in MetS and control. MetS, metabolic syndrome; NS, not significant.