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

J Gastroenterol Hepatol. 2005 Jul;20(7):1102-8. doi: 10.1111/j.1440-1746.2005.03860.x.

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alleles
  • DNA / genetics*
  • Disease Progression
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Markers
  • Genotype
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / enzymology*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Liver Cirrhosis / enzymology*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 3 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Retrospective Studies

Substances

  • Genetic Markers
  • DNA
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1