title: Cyclooxygenase-2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Department of Medicine Clinical Research Laboratory, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakaki
authors.forename: Reiko
authors.initials: R
authors.lastname: Makino
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hiroishi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Junichi
authors.initials: J
authors.lastname: Eguchi
authors.forename: Ayako
authors.initials: A
authors.lastname: Hiraide
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doi
authors.forename: Risa
authors.initials: R
authors.lastname: Omori
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari