Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
J Viral Hepat. 2012 Sep;19(9):608-14. doi: 10.1111/j.1365-2893.2011.01580.x. Epub 2012 Jan 28.
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.
环氧化酶（COX）-2 参与炎症、抗凋亡和致癌作用。COX-2 启动子中单核苷酸多态性（SNP）的-1195GG 基因型与慢性丙型肝炎患者血小板计数降低有关。已报道载脂蛋白样磷脂酶结构域蛋白 3（PNPLA3）基因（rs738409C>G）的多态性与肝硬化有关，IL-28B 附近 SNP 的主要基因型与病毒清除有关。本研究旨在评估这些 SNP 对慢性丙型肝炎患者疾病进展的贡献。本研究纳入了 220 例日本慢性丙型肝炎患者。为了分析这些 SNP 与肝纤维化和炎症的关系，对-1195COX-2、PNPLA3 和 IL28B（rs8099917）三个 SNP 进行了基因分型。COX-2 的-1195GG 基因型与肝纤维化进展和肝脏组织中炎症水平升高有关。IL28B 的主要基因型也与肝纤维化进展有关，但 PNPLA3 的多态性与纤维化和炎症均无关。多变量分析显示，COX-2 的-1195GG 是与肝纤维化进展相关的独立因素，而 IL28B 的主要基因型和 HCV 基因型 2 是其他独立因素。综上所述，COX-2 的-1195GG 基因型是肝脏疾病进展的遗传标志物，而 PNPLA3 基因型与日本慢性丙型肝炎患者的疾病进展无关。
