title: Genetic polymorphism in cyclooxygenase-2 promoter affects hepatic inflammation and fibrosis in patients with chronic hepatitis C.
abstract: Cyclooxygenase (COX)-2 is involved in inflammation, anti-apoptosis and carcinogenesis. The -1195GG genotype of single nucleotide polymorphism (SNP) in COX-2 promoter was associated with low platelet counts in patients with chronic hepatitis C. Polymorphism of patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene (rs738409 C>G) have been reported to be associated with cirrhosis, and the major genotype of SNPs near interleukin (IL)28B are related to viral clearance. The present study was designed to assess the contribution of these SNPs to disease progression in patients with chronic hepatitis C. The study enrolled 220 Japanese patients with chronic hepatitis C. Three SNPs, -1195 COX-2, PNPLA3 and IL28B (rs8099917), were genotyped in order to analyze their association with hepatic fibrosis and inflammation. The -1195GG genotype in COX-2 was associated with advanced fibrosis and higher levels of inflammation in the liver tissues. The major genotype of IL28B was also associated with advanced fibrosis, but the polymorphism of PNPLA3 was neither associated with fibrosis nor inflammation. Multivariate analysis showed that -1195GG in COX-2 is an independent factor associated with advanced fibrosis, while the major genotype of IL28B and HCV genotype 2 were other independent factors. In conclusion, the -1195GG genotype in COX-2 is a genetic marker for liver disease progression, while the PNPLA3 genotypes are not associated with disease progression in Japanese patients with chronic hepatitis C.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Miyashita
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kajiwara
authors.forename: Hisako
authors.initials: H
authors.lastname: Nozawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hiroishi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
mesh_terms: D044466:Asian People; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D051546:Cyclooxygenase 2; D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent