Association of genetic variants of the chemokine receptor MRS and its ligands, RANTES and MCP-2, with outcome of HCV infection
Association of genetic variants of the chemokine receptor MRS and its ligands, RANTES and MCP-2, with outcome of HCV infection
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DOI：
10.1016/j.hep.2003.09.027
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发表时间：
2003-12-01
期刊：
影响因子：
13.5
通讯作者：
Hill, AVS
中科院分区：
文献类型：
--
作者：
Hellier, S;Frodsham, AJ;Hill, AVS
宿主基因变异对丙型肝炎病毒感染和治疗结局的影响尚不清楚。趋化因子受体CCR5、CCR2和CCR3及其配体RANTES、MCP-1、MCP-2和MIP-1α参与了丙型肝炎病毒感染时的免疫反应和淋巴细胞向肝脏的选择性募集。我们研究了这些基因中的20个多态，并在一个大型的欧洲队列中调查了它们与持续携带丙型肝炎病毒、肝病严重程度、肝脏炎症和治疗反应的关系。CCR5-Delta32与门脉炎症减轻(P=.011，优势比[OR]：2.3，95%可信区间[CI]：1.09-4.84)和较轻的纤维化(P=0.015，OR：1.97，95%CI：1.13-3.42)显著相关。RANTES基因-403位启动子多态与门脉炎症程度较轻相关(P=0.004)。MCP2基因Q46K的氨基酸改变与肝纤维化的严重程度相关(P=0.018，OR：2.29，95%CI：1.14-4.58)。总之，我们的研究提示CCR5-Delta32、RANTES-403和MCP-2Q46K基因多态可能在丙型肝炎病毒感染的结局中起作用。
The effect of host genetic variation on the outcome of hepatitis C virus (HCV) infection and its treatment is poorly understood. The chemokine receptors CCR5, CCR2, and CCR3 and their ligands, RANTES, MCP-1, MCP-2, and MIP-1alpha, are involved in the immune responses and the selective recruitment of lymphocytes to the liver in HCV infection. We studied 20 polymorphisms within these genes and investigated their association with persistent carriage of HCV, severity of liver disease, hepatic inflammation, and response to treatment in a large European cohort. Significant associations were found between CCR5-Delta32 and reduced portal inflammation (P = .011, odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.09-4.84) and milder fibrosis (P = .015, OR: 1.97, 95% CI: 1.13-3.42). A promoter polymorphism at position -403 in the RANTES gene was associated with less severe portal inflammation (P = .004). An amino acid change in MCP2, Q46K, was associated with severity of fibrosis (P = .018, OR: 2.29,95% CI: 1.14-4.58). In conclusion, our study suggests a possible role of the polymorphisms CCR5-Delta32, RANTES -403, and MCP-2 Q46K in the outcome of HCV infection.