基因1b型慢性丙型肝炎患者抗病毒治疗前氨基酸序列分析  

Mutations in hepatitis C virus genotype 1b before antiviral therapy

作　　者：傅涓涓[1] 孔玮晶[1] 蒋栋[2] 魏来[2] 潘修成[1] 

机构地区：[1]徐州医学院附属医院感染病科,江苏省221006 [2]北京大学人民医院肝病研究所

出　　处：《江苏医药》2014年第5期519-522,共4页Jiangsu Medical Journal

基　　金：国家"十一五"丙肝研究队列的延续观察(2012ZX10002003-004)

摘　　要：目的探讨基因1b型慢性丙型肝炎(CHC)患者氨基酸序列变异与聚乙二醇干扰素α-2a(PegIFNα-2a)联合利巴韦林(RBV)抗病毒治疗疗效的关系。方法 18例应用PegIFNα-2a/RBV抗病毒治疗48周的基因1b型CHC患者中,9例为快速应答,9例为无应答。应用RT-PCR法扩增接近全长的HCV基因组序列,用克隆测序方法进行核苷酸序列测定,在氨基酸水平比较两组序列的差别。结果没有发现与治疗应答相关的单个氨基酸变异,且系统进化分析未显示与应答相关的变异簇集现象。进一步比对发现,NS5B区尤其是部分拇指区域的氨基酸序列(aa 371-458)及NS5A-V3区(aa 384-407)氨基酸突变数目与PegIFNα-2a联合RBV抗病毒应答情况相关(P<0.01和P<0.05)。NS5B区氨基酸突变数目与V3区氨基酸突变数目存在正相关(r=0.568,P<0.05)。结论 NS5B区尤其是部分拇指区域的氨基酸突变数目及V3区氨基酸突变数目与干扰素疗效可能相关。Objective To investigate the association of the amino acid variation in the patients with HCV genotype lb and the response to PegIFNα-2a and RBV combination therapy. Methods Eighteen patients infected with HCV genotype-lb were treated with PegIFNα-2a plus RBV for 48 weeks, of whom 9 cases had a rapid virological response and 9 cases had non-response. The nearly full- length HCV genome sequence was amplified, cloned and sequenced. Genetic diversity differences between two groups were analyzed, Results No therapeutic response-related single amino acid variation and variation gathering were seen. However, the number of amino acid mutation in the NS5B region,especially in the thumb domain and in the NSSA-V3 region, was associated with the response to PegIFNα/RBV therapy（P〈0. 01 and P〈0. 05）. The number of substitutions in the NS5B region was positively correlated with the number of substitutions in the V3 region （r=0. 568, P〈0. 05）. Canclusion The number of amino acid mutations in the NS5B region,especially in the thumb domain and the NSSA-V3 region, is correlated with the response to combined PegIFNα-2a and RBV therapy in HCV-lb patients.

关 键 词：慢性丙型肝炎 聚乙二醇干扰素Α 利巴韦林 

分 类 号：R512[医药卫生—内科学]