HLA-DP基因多态性与HCV患者抗病毒治疗免疫应答的相关性分析
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篇名: HLA-DP基因多态性与HCV患者抗病毒治疗免疫应答的相关性分析
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摘要: 目的:研究HLA-DP基因多态性与丙型肝炎病毒(HCV)患者抗病毒治疗免疫应答的相关性。方法:选取2013年5月-2017年8月于我院就诊的HCV汉族患者106例,所有患者均接受为期48周的聚乙二醇化干扰素α(PEG IFNα)+利巴韦林(RBV)联合治疗,并于停药后接受为期24周的随访。记录其年龄、体质量、HCV-RNA基线水平等一般资料,并采用Taqman-MGB荧光探针实时定量聚合酶链反应法检测其HLA-DP基因rs3077、rs2395309位点的分型。根据治疗结局将患者分为持续病毒学应答组(SVR)和未持续病毒学应答组(N-SVR),采用Logistic回归模型对影响HCV患者抗病毒治疗免疫应答的相关因素(性别、年龄、体质量指数、HCV-RNA基线水平以及基因多态性)进行单因素和多因素分析。结果:106例患者中,rs3077位点CC、CT、TT型频率分别为40.6%、35.8%、23.6%,rs2395309位点GG、GA、AA型频率分别为50.0%、39.6%、10.4%,均符合Hardy-Weinberg遗传平衡(P>0.05)。SVR组患者80例,N-SVR组患者26例;SVR组患者的年龄、rs3077位点CT、TT型以及rs2395309位点GA、AA型比例均显著低于N-SVR组,rs3077位点CC型以及rs2395309位点GG型比例均显著高于N-SVR组(P<0.05);而两组患者的性别、体质量指数、HCV-RNA基线水平比较,差异均无统计学意义(P>0.05)。单因素、多因素分析结果显示,患者性别,体质量指数,HCV-RNA基线水平,rs3077位点CC型、rs2395309位点GG型与其抗病毒治疗免疫应答不显著相关(P>0.05),而年龄、rs3077位点CT和TT型、rs2395309位点GA和AA型与其抗病毒治疗免疫应答显著相关[比值比(OR)分别为1.135、1.766、1.283、1.218、1.103,95%置信区间(CI)分别为(1.017,1.267)、(1.007,3.100)、(1.038,1.585)、(1.011,1.467)、(1.038,1.172),P<0.05]。结论:年龄以及HLA-DP基因rs3077、rs2395309位点多态性与HCV汉族患者PEG IFNα+RBV抗病毒治疗免疫应答相关,其中低龄患者可能获得较高的抗病毒免疫应答率,而T、A突变等位基因携带者则可能获得更低的抗病毒免疫应答率。
ABSTRACT: OBJECTIVE: To study the correlation of HLA-DP gene polymorphisms with the immune response to antiviral treatment for hepatitis C virus (HCV) patients. METHODS: A total of 106 HCV Han-nationality patients were collected from our hospital during May 2013 to Aug 2017. All patients received PEG IFNα+ribavirin (RBV) for 48 weeks, and then 24 week follow-up after drug withdrawal. Age, body weight and baseline level of HCV-RNA were recorded. The typing of rs3077 and rs2395309 site of HLA-DP gene were detected by RT-qPCR with Taqman-MGB fluorescent probe. According to treatment outcome, the patients were divided into two groups such as sustained viral response (SVR) group and no-sustained viral response (N-SVR) group. Univariate and multivariate analysis were performed for influential factors (gender, age, body weight index, HCV-RNA baseline level, gene polymorphisms) of immune response to antiviral treatment for HCV patients with Logistic regression model. RESULTS: Among 106 patients, the frequencies of CC, CT and TT genotype at rs3077 site were 40.6%, 35.8% and 23.6%; those of GG, GA and AA genotype at rs2395309 site were 50.0%, 39.6%, 10.4%, respectively, which were in line with Hardy-Weinberg genetic balance (P>0.05). Totally 80 HCV patients were obtained in SVR group, and 26 HCV patients in N-SVR group. The patient’s age, the proportion of CT and TT genotype of rs3077 site and GA and AA genotype of rs2395309 site in SVR group were significantly lower than N-SVR group. The proportion of CC genotype at rs3077 site and GG genotype at rs2395309 site were significantly higher than N-SVR group (P<0.05). There was no statistical significance in gender, body weight index or HCV-RNA baseline level between 2 groups (P>0.05). Univariate and multivariate analysis showed that gender, body mass index, HCV-RNA baseline level, CC genotype at rs3077 site and GG genotype at rs2395309 site were not related to the immune response to antiviral treatment (P>0.05). Age, CT and TT genotype at rs3077 site, GA and AA genotype at rs2395309 site were associated with the immune response to antiviral therapy [OR were 1.135, 1.766, 1.283, 1.218, 1.103, 95%CI were (1.017,1.267), (1.007,3.100), (1.038,1.585), (1.011,1.467), (1.038,1.172), respectively, P<0.05]. CONCLUSIONS: Age and the polymorphisms of HLA-DP gene at rs3077 and rs2395309 site are related to immune response to PEG IFNα+RBV antiviral treatment for HCV Han-nationality patients. Young patients may have higher antiviral immune response rate, while carriers with T and A mutation alleles may have lower antiviral immune response rate.
期刊: 2019年第30卷第22期
作者: 石菡,李艳芳,袁媛,贾志华,纪风兵
AUTHORS: SHI Han,LI Yanfang,YUAN Yuan,JIA Zhihua,JI Fengbing
关键字: 丙型肝炎病毒;汉族;HLA-DP基因;基因多态性;rs3077;rs2395309;抗病毒治疗免疫应答;相关性
KEYWORDS: Hepatitis C virus; Han nationality; HLA-DP gene; Gene polymorphisms; rs3077; rs2395309; Antiviral treatment immune response; Correlation
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