Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype
Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype
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DOI：
10.1007/s00109-003-0493-0
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发表时间：
2003-12-01
影响因子：
4.7
通讯作者：
Kallinowski, B
中科院分区：
文献类型：
--
作者：
Gehrke, SG;Stremmel, W;Kallinowski, B
慢性丙型肝炎的轻度铁超载与肝纤维化、丙型肝炎病毒(丙型肝炎病毒)1b型感染以及对干扰素治疗的反应受损有关。在这项研究中，我们评估了血色素沉着症基因HFE和转铁蛋白受体基因TFR1的多态是否与这些典型的发现有关。检测246例丙型肝炎病毒感染者和200例献血员的C282Y、H63D和S65C突变(HFE)和S142G多态(TFR1)。检测丙型肝炎病毒基因分型、血清铁蛋白水平、肝内可染铁含量、以及根据METAVIR评分(F0-F4)的肝纤维化分级。在丙型肝炎病毒感染的患者中，HFE中C282Y突变的杂合子与血清铁蛋白水平升高、肝铁染色以及晚期纤维化或肝硬变(F2-F4)显著相关。经多因素Logistic回归分析，携带C282Y杂合子和C282Y/H63D和C282Y/S65C复合杂合子的丙型肝炎病毒感染者发生晚期纤维化或肝硬变(F2-F4)的优势比分别为2.5和4.8。HFE中C282Y突变的杂合性与慢性丙型肝炎患者铁蓄积和纤维化进展有关。
Mild iron overload in chronic hepatitis C is associated with liver fibrosis, hepatitis C virus (HCV) genotype 1b infection, and an impaired response to interferon therapy. In this study we evaluated whether polymorphisms in the hemochromatosis gene HFE and the transferrin receptor gene TFR1 are associated with these typical findings. The study considered 246 HCV-infected patients and 200 blood donors as controls, in which C282Y, H63D, and S65C mutations (HFE) and the S142G polymorphism (TFR1) were detected. HCV genotype, serum ferritin levels, stainable intrahepatic iron, and grade of fibrosis according to the METAVIR score (F0-F4) were determined. In HCV-infected patients, heterozygosity for the C282Y mutation in HFE was significantly associated with elevated serum ferritin levels, stainable liver iron, and advanced fibrosis or cirrhosis (F2-F4). By multivariate logistic regression analysis the odds ratio for the development of advanced fibrosis or cirrhosis (F2-F4) was 2.5 for HCV-infected patients carrying a heterozygous C282Y mutation and 4.8 for HCV-infected patients with C282Y/H63D and C282Y/S65C compound heterozygosity. Heterozygosity for the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C.