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Genetic polymorphism in cyclooxygenase‐2 promoter affects hepatic inflammation and fibrosis in patients with chronic hepatitis C
Author(s) -
Miyashita Miyuki,
Ito Takayoshi,
Sakaki Masashi,
Kajiwara Atsushi,
Nozawa Hisako,
Hiroishi Kazumasa,
Kobayashi Mariko,
Kumada Hiromitsu,
Imawari Michio
Publication year - 2012
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2011.01580.x
Subject(s) - single nucleotide polymorphism , genotype , fibrosis , snp , cirrhosis , inflammation , immunology , medicine , liver disease , biology , gastroenterology , gene , genetics
Summary. 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.