期刊
HEPATOLOGY RESEARCH
卷 40, 期 12, 页码 1219-1226出版社
WILEY
DOI: 10.1111/j.1872-034X.2010.00727.x
关键词
cyclooxygenase-2; forkhead box protein 3; hepatitis C virus; osteopontin; single nucleotide polymorphisms
资金
- Ministry of Health, Labor and Welfare, Japan
Aim: Because polymorphisms of cyclooxygenase-2 (COX-2) and osteopontin (OPN) promoter regions and a promoter/enhancer region of forkhead box protein 3 (FOXP3) gene are known to affect immune responses, we examined whether these polymorphisms can influence susceptibility to hepatitis C virus (HCV) infection and progression of liver disease. Methods: Peripheral blood samples were obtained from 104 Japanese patients with chronic HCV infection and 74 healthy Japanese donors. Polymerase chain reaction single-stranded conformational polymorphism analysis of genomic DNA was performed to determine the polymorphisms. Results: The risk of persistent HCV infection was decreased in subjects with -1195GG genotype of the COX-2 promoter region. However, in patients with chronic HCV infection, the -1195GG genotype was associated with advanced-stage liver disease. A luciferase reporter assay performed to analyze the effect of single nucleotide polymorphisms (SNP) (-1195A or -1195G) in COX-2 gene on transcriptional activity using the HepG2, Huh7 and HeLa cell lines indicated that the -1195G genotype showed higher transcriptional activity than the -1195A genotype. SNP of OPN and FOXP3 did not differ between patients with chronic HCV infection and controls. However, the -443TT genotype of the OPN promoter region was associated with increased inflammatory activity of the liver. Conclusion: These results suggest that the -1195GG genotype of the COX-2 promoter region protects against HCV infection in the Japanese. However, once chronic infection is established, the -443TT genotype of the OPN promoter region and the -1195GG genotype of the COX-2 promoter are thought to promote inflammation and contribute to the progression of liver disease.
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