| Cyclooxygenase-2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression. | |
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MedLine Citation:
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PMID: 20880066 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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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Authors:
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Masashi Sakaki; Reiko Makino; Kazumasa Hiroishi; Kumiko Ueda; Junichi Eguchi; Ayako Hiraide; Hiroyoshi Doi; Risa Omori; Michio Imawari |
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Publication Detail:
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Type: Journal Article Date: 2010-09-28 |
Journal Detail:
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Title: Hepatology research : the official journal of the Japan Society of Hepatology Volume: 40 ISSN: 1386-6346 ISO Abbreviation: Hepatol. Res. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9711801 Medline TA: Hepatol Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1219-26 Citation Subset: - |
Copyright Information:
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© 2010 The Japan Society of Hepatology. |
Affiliation:
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Division of Gastroenterology, Department of Medicine Clinical Research Laboratory, Showa University School of Medicine, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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