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The association offunctional gene polymorphisms with tbe progression of liver fibrosis in chronic hepatitis C.

功能基因多态性与慢性丙型肝炎肝纤维化进展的关系.

基本信息

批准号：
17590641
负责人：
MURAWAKI Yoshikazu
金额：
$ 2.43万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590641/
关键词：
chronic hepatitis liver fibrosis genotype MMP-1 MMP-3 MMP-9 TGF-β1 IL-1β MMP-2 MMP-7 IL-1RN IL-1B

项目摘要

In chronic hepatitis C, the interindividual difference in responses against the hepatic necroinflammation appears to be important in the progression of liver fibrosis. This study was to examine the possible association of MMP-1 -1607 1G/2G, MMP-2. -1306 C/T, MMP-3 -1171 5A/6A, MMP-7 -181 A/G, MMP-9 -1562 T/C, TGF-βl +819 T/C, IL-lβ -511 C/T, IL-1RN VNTR polymorphisms with the progression of liver fibrosis in Japanese patients with hepatitis C virus-related chronic liver disease, using cross-sectional and longitudinal study designs. We examined 93 chronic hepatitis C patients and 90 liver cirrhosis C patients. The chronic hepatitis patients were divided into progressive fibrosis and non-progressive fibrosis groups. Gene lymorphisms were analyzed using a polymerase-chain reaction-based assay. In the cross-sectional study, the MMP-1 2G/2G homozygotes and MMP-9 C/C homozygotes were significantly more in cirrhosis group than in chronic hepatitis group, whereas other genotypes showed no significant differences. In the longitudinal study, MMP-3 5A carriers and TGF-β1 T carriers were significantly more in the progressive fibrosis group than in non-progressive fibrosis group, whereas other genotypes showed no significant differences. These findings suggest that MMP-1, MMP-3, MMP-9 and TGF-131 genotypes account for some of the variability in the progression of chronic hepatitis C.

在慢性丙型肝炎中，对肝脏坏死性炎症反应的个体间差异在肝纤维化的进展中似乎是重要的。本研究旨在探讨基质金属蛋白酶-1-1607 1G/2G、基质金属蛋白酶-2之间的关系。-1306C/T、MMP3-11715A/6A、MMP7-181A/G、MMP9-1562T/C、转化生长因子-βL+819T/C、IL-Lβ-511C/T、IL-1RNVNTR基因多态性与日本丙型肝炎病毒相关性慢性肝病患者肝纤维化的进展。我们检测了93例慢性丙型肝炎患者和90例丙型肝炎肝硬化患者。慢性肝炎患者分为进展性纤维化组和非进展性纤维化组。用基于聚合酶链式反应的方法分析基因的裂解情况。在横断面研究中，肝硬化组中MMP1的2G/2G纯合子和MMP9的C/C纯合子显著多于慢性肝炎组，而其他基因型的差异无统计学意义。在纵向研究中，进展性纤维化组MMP35A携带者和转化生长因子β1T携带者显著多于非进展性纤维化组，其他基因型差异无统计学意义。这些发现表明，在慢性丙型肝炎的进展过程中，有一些变异是由基质金属蛋白酶-1、基质金属蛋白酶-3、基质金属蛋白酶-9和转化生长因子-131基因引起的。