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

发布时间：2018-03-08 17:16

本文选题：慢性丙型肝炎　切入点：干扰素　出处：《天津医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：探讨慢性丙型肝炎(CHC)患者的α干扰素受体1(IFNAR1)基因启动子的单核苷酸多态性与干扰素(IFN)α抗HCV治疗应答之间的关系。方法： 1.选择应用聚乙二醇干扰素α (Peg-IFN α)联合利巴韦林(RBV)抗病毒治疗的慢性丙型肝炎患者73例,治疗前行HCV RNA定量、HCV基因型、谷丙转氨酶(ALT)等检测,疗程48周,根据应答情况分为应答组与无应答组。 2.对入选患者IFNAR1启动子区基因进行PCR扩增及双向测序。结果： 1.抗病毒疗效：在应用聚乙二醇干扰素α联合利巴韦林抗病毒治疗的73例患者中应答组47例(64.39%),无应答组26例(35.61%),应答组与无应答组的性别、年龄、治疗前ALT及HCV基因型的差异无统计学意义。而治疗前HCVRNA PCR定量比较,两组的差异有统计学意义,P=0.003。 2.在IFNAR1基因启动子区测序发现-568、-408、-77、-3四个位点存在基因多态性,分别为：-568G/C、-408C/T、-3C/T及-77GT双核苷酸重复序列(-77(GT)n),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(52.054%和15.068%)。 3.IFNAR1启动子基因型与抗病毒治疗的应答率的关系：非-568C/-408C/-77(GT)5/-3C者的抗病毒应答率为77.1%,高于-568C/-408C/-77(GT)5/-3C者56.2%(x2=4.773, P=0.029);-568C/-408T/-77(GT)5/-3T者的应答率90.9%,高于非568C/-408T/-77(GT)5/-3T者59.7%(X2=3.92,P=0.048)。结论： IFNAR1启动子基因型为-568C/-408T/-77(GT)5/-3T或非-568C/-408C/-77(GT)5/-3C者对IFN-α为基础的抗病毒治疗能产生更好的应答,患者IFNAR1启动子基因多态性可能与IFN α抗HCV治疗应答有关。
[Abstract]:Objective:. To investigate the relationship between the single nucleotide polymorphism of interferon 伪 receptor 1 (IFNAR1) gene promoter and the anti HCV response of interferon (IFN) 伪 in patients with chronic hepatitis C (HCV). Methods:. 1. 73 patients with chronic hepatitis C who were treated with peginterferon 伪 (Peg-IFN 伪) and ribavirin (RBV) were selected. The HCV RNA genotypes and alt were measured before treatment for 48 weeks. According to the response, it is divided into two groups: the responding group and the non-responding group. 2. The IFNAR1 promoter gene was amplified by PCR and sequenced. Results:. 1. Antiviral efficacy: in 73 patients treated with peginterferon 伪 and ribavirin, 47 patients in the response group and 26 patients in the non-response group were treated with ribavirin. There was no significant difference in ALT and HCV genotypes before treatment, but there was a significant difference in HCVRNA PCR between the two groups before treatment (P 0.003). 2. In the promoter region of IFNAR1 gene, four loci were found to be polymorphic, namely: -568G / C / -408C / -408C / T and -77GT dinucleotide repeats, with a total of 10 gene haplotypes, among which -568C / -408C / -408T / -408T / -408T / -708T and -568C / -408T / -408T / -408T / -568C / -408T / -408T and -568C / -408T / -408T / -777- 3T, respectively, were found to have the highest frequency of gene haplotypes (-568C / -408C / -408T / -408T / -408T / -408T / -408T / -7773T). 3. The relationship between IFNAR1 promoter genotype and the response rate of antiviral therapy: the response rate of non-568C / 408C / -408C / -77GT5 / -3C was 77.1, higher than that of -568C-408C-408C-77GT5 / 3C 56.2x24.773, P0.02929C / 408T / 408T / 408T / 77GT5r-3T, higher than that of non-568C- / -408T- 77GT5-3T, 59.7Cr-77GT5-3T = 59.7C- / -77GT5-3T / 59.7C- / -408T / -408T / -408T- 77GT5-3T, 59.7C- / -77GT5-3T respectively. Conclusion:. The genotype of IFNAR1 promoter was -568C / -408T / -77G 5 / -3T or non-568C / -408C / -408C / -77T / -3C, which could produce a better response to IFN- 伪 based antiviral therapy. The polymorphism of IFNAR1 promoter gene in patients may be related to the anti-#en3# response of IFN 伪.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.63

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