慢性丙型肝炎患者Ⅰ型干扰素受体启动子基因多态性与抗病毒疗效的关系

Association between the type Ⅰinterferon receptor promoter gene and treatment response to antivirus in patients with chronic hepatitis C

目的研究慢性丙型肝炎(CHC)患者Ⅰ型干扰素受体之一IFNAR1启动子基因的单核苷酸多态性与干扰素(IFN)α抗HCV疗效的关系。方法应用聚乙二醇干扰素α联合利巴韦林抗HCV治疗,根据抗病毒疗效将73例患者分为应答组与无应答组,并对其IFNAR1启动子基因进行扩增及测序。结果 73例患者中应答组47例,无应答组26例,在-568、-408、-77、-3位点发现基因多态性,共10种基因单体型,其中单体型-568C/-408C/-77(GT)5/-3C和-568C/-408T/-77(GT)5/-3T出现频率最高。非-568C/-408C/-77(GT)5/-3C者的抗病毒应答率77.1%高于-568C/-408C/-77(GT)5/-3C者52.6%,(χ2=4.773,P=0.029),-568C/-408T/-77(GT)5/-3T者的抗病毒应答率90.9%高于非-568C/-408T/-77(GT)5/-3T者59.7%,(χ2=3.92,P=0.048)。结论 CHC患者IFNAR1启动子基因多态性可能影响IFNα抗HCV治疗应答。

Objective To investigate the association between polymorphisms of type Ⅰinterferon receptor（IFNAR1） promoter gene and the treatment response to interferon alpha（IFNα） in patients with chronic hepatitis C（CHC）.Methods 73 CHC patients who consented to receive pegylated IFNα in combination with ribavirin therapy were enrolled in this study.The treatment responses were monitored.The subjects were divided into two groups as response and no response.Meanwhile,the genes of IFNAR1 promoter in these patients were sequenced.Measurement data were analyzed by t test and enumeration data were analyzed by Chi square test.Results 47 patients achieved response and 26 patients had no response.Polymorphisms were identified in IFNAR1 promoter gene,which include G/C substitution at locus-568,C/T substitution at locus-408,C/T substitution at locus-3 and GT microsatellite repeat sequence at locus-77.The response rate to antivirus therapy in CHC patients with haplotype non-568C/-408C/-77（GT）5/-3C was higher than that in patients with haplotype-568C/-408C/-77（GT）5/-3C（77.1% vs 52.6%,χ2=4.773,P=0.029）.The response rate to antivirus therapy in CHC patients with haplotype-568C/-408T/-77（GT）5/-3T was higher than that in patients with haplotype non-568C/-408T/-77（GT）5/-3T（90.9% vs 59.7%,χ2=3.92,P=0.048）.Conclusion Polymorphisms of IFNAR1 promoter gene are associated with the treatment response to IFNα in CHC patients.