HCV核心蛋白氨基酸替换与干扰素应答的关系

发布时间：2018-03-25 10:52

本文选题：核心蛋白　切入点：丙型肝炎病毒　出处：《第三军医大学学报》2013年09期

【摘要】：目的研究慢性丙型肝炎病毒核心蛋白氨基酸替换与干扰素疗效的关系。方法纳入HCV RNA阳性的慢性丙型肝炎患者108例,依据干扰素治疗结局分为持续病毒学应答组(76例)、非持续病毒学应答组(32例)。逆转录巢式PCR(RT-nested-PCR)扩增核心蛋白区,分析其氨基酸替换模式及其与干扰素疗效的关系。结果高频替换(频率10%)发生于Core蛋白第70、75、91、106、110、147、187位氨基酸残基,各位点之间存在广泛的连锁替换;两组间Core蛋白第70位的Q/non-Q替换(P=0.004)、91位的M/non-M替换(P=0.039)、110位的T/non-T替换(P=0.025)具有显著差异;70Q、91M、110T替换更倾向于发生不应答治疗结局,OR值及95%CI分别为0.288(0.120～0.693)、0.413(0.177～0.966)、0.346(0.133～0.896);同时携有上述2个以上的"抵抗型"替换者,治疗4周时HCV RNA水平下降更缓慢(P=0.001)。结论 HCV Core区第70、91、110三个位点可作为Core区预测干扰素疗效的优选氨基酸位点。
[Abstract]:Objective to study the relationship between amino acid replacement of core protein of chronic hepatitis C virus and the efficacy of interferon. Methods 108 patients with chronic hepatitis C with HCV RNA positive were included. According to the treatment outcome, interferon was divided into two groups: persistent virological response group (n = 76) and nonpersistent virological response group (n = 32). Reverse transcription-nested PCR RT nested PCR was used to amplify the core protein region. Results the high frequency substitution (frequency 1010) occurred in the amino acid residues at the 701106110147187 of Core protein, and there were extensive linkage substitutions among the sites. There was a significant difference between the two groups in the Q/non-Q replacement (P0. 004) and the M/non-M replacement (P0. 039 / 110) in the 70th position of Core protein (P 0. 025). The odds ratio (OR) and 95%CI were 0. 2888 0. 120 0. 693C and 0. 34660.1330.896, respectively, and there were more than 2 "resistant" replacers with the above two "resistant" replacements. After 4 weeks of treatment, the level of HCV RNA decreased more slowly. Conclusion the 70,91110 site of HCV Core region can be used as the optimal amino acid site for predicting the therapeutic effect of interferon in Core region.
【作者单位】：第三军医大学西南医院全军感染病研究所感染病研究重庆市重点实验室;泸州医学院附属医院感染科;
【基金】：“十一五”国家科技重大专项(2012ZX10001003-003-003,2011ZX09302-005)~~
【分类号】：R373.21

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