Association of functional gene polymorphisms of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐9 with the progression of chronic liver disease

Abstract

Matrix metalloproteinases (MMP) play an important role in the progression of liver fibrosis in addition to fibrogenesis. MMP-1, MMP-3, and MMP-9 gene polymorphisms have been shown to influence the transcriptional activity of their respective gene promoter in an allele-specific manner. The aim of this study was to examine the possible association of MMP-1, MMP-3, and MMP-9 gene polymorphisms with the progression of chronic liver disease in the Japanese population. We examined 91 patients with HCV-related chronic hepatitis and 89 patients with HCV-related liver cirrhosis. We determined MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms using polymerase-chain reaction based assays. In MMP-1 genotypes, the 2G homozygotes were significantly more in cirrhotic group than in chronic hepatitis group. In MMP-3 genotypes, there were no significant differences in genotype distributions and allele frequencies between chronic hepatitis and liver cirrhosis groups. However, 5A carriers had a significantly lower age at liver cirrhosis diagnosis and a higher Child-Pugh score compared with the 6A homozygotes. In MMP-9 genotypes, the C homozygotes and C allele frequencies were significantly more in liver cirrhosis group than in chronic hepatitis group. These findings suggest that MMP-1, MMP-3, and MMP-9 gene polymorphisms account for some of the variability in the progression of HCV-related chronic liver diseases.