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

Okamoto K, Mimura K, Murawaki Y, Yuasa I

Division of Medicine and Clinical Science, Tottori University School of Medicine, Yonago, Japan.

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.

Published 15 June 2005 in J Gastroenterol Hepatol, 20(7): 1102-8.
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