本文選題：慢性丙型肝炎　切入點(diǎn)：干擾素　出處：《天津醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：目的： 探討慢性丙型肝炎(CHC)患者的α干擾素受體1(IFNAR1)基因啟動(dòng)子的單核苷酸多態(tài)性與干擾素(IFN)α抗HCV治療應(yīng)答之間的關(guān)系。 方法： 1.選擇應(yīng)用聚乙二醇干擾素α (Peg-IFN α)聯(lián)合利巴韋林(RBV)抗病毒治療的慢性丙型肝炎患者73例,治療前行HCV RNA定量、HCV基因型、谷丙轉(zhuǎn)氨酶(ALT)等檢測(cè),療程48周,根據(jù)應(yīng)答情況分為應(yīng)答組與無應(yīng)答組。 2.對(duì)入選患者IFNAR1啟動(dòng)子區(qū)基因進(jìn)行PCR擴(kuò)增及雙向測(cè)序。 結(jié)果： 1.抗病毒療效：在應(yīng)用聚乙二醇干擾素α聯(lián)合利巴韋林抗病毒治療的73例患者中應(yīng)答組47例(64.39%),無應(yīng)答組26例(35.61%),應(yīng)答組與無應(yīng)答組的性別、年齡、治療前ALT及HCV基因型的差異無統(tǒng)計(jì)學(xué)意義。而治療前HCVRNA PCR定量比較,兩組的差異有統(tǒng)計(jì)學(xué)意義,P=0.003。 2.在IFNAR1基因啟動(dòng)子區(qū)測(cè)序發(fā)現(xiàn)-568、-408、-77、-3四個(gè)位點(diǎn)存在基因多態(tài)性,分別為：-568G/C、-408C/T、-3C/T及-77GT雙核苷酸重復(fù)序列(-77(GT)n),共10種基因單體型,其中單體型-568C/-408C/-77(GT)5/-3C和-568C/-408T/-77(GT)5/-3T出現(xiàn)頻率最高(52.054%和15.068%)。 3.IFNAR1啟動(dòng)子基因型與抗病毒治療的應(yīng)答率的關(guān)系：非-568C/-408C/-77(GT)5/-3C者的抗病毒應(yīng)答率為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者的應(yīng)答率90.9%,高于非568C/-408T/-77(GT)5/-3T者59.7%(X2=3.92,P=0.048)。 結(jié)論： IFNAR1啟動(dòng)子基因型為-568C/-408T/-77(GT)5/-3T或非-568C/-408C/-77(GT)5/-3C者對(duì)IFN-α為基礎(chǔ)的抗病毒治療能產(chǎn)生更好的應(yīng)答,患者IFNAR1啟動(dòng)子基因多態(tài)性可能與IFN α抗HCV治療應(yīng)答有關(guān)。
[Abstract]:Objective:. To investigate the relationship between the single nucleotide polymorphism of interferon 偽 receptor 1 (IFNAR1) gene promoter and the anti HCV response of interferon (IFN) 偽 in patients with chronic hepatitis C (HCV). Methods:. 1. 73 patients with chronic hepatitis C who were treated with peginterferon 偽 (Peg-IFN 偽) 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 偽 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- 偽 based antiviral therapy. The polymorphism of IFNAR1 promoter gene in patients may be related to the anti-#en3# response of IFN 偽.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R512.63

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