【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。更多还原

【Abstract】 Objective To investigate the association of the amino acid variation in the patients with HCV genotype 1band the response to PegIFNα-2aand RBV combination therapy.Methods Eighteen patients infected with HCV genotype-1bwere treated with PegIFNα-2aplus RBV for 48 weeks,of whom 9cases had a rapid virological response and 9cases had non-response.The nearly fulllength 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 NS5A-V3region,was associated with the response to PegIFNα/RBV therapy(P<0.01and P<0.05).The number of substitutions in the NS5Bregion was positively correlated with the number of substitutions in the V3region(r=0.568,P<0.05). Conclusion The number of amino acid mutations in the NS5Bregion,especially in the thumb domain and the NS5A-V3region,is correlated with the response to combined PegIFNα-2aand RBV therapy in HCV-1bpatients.更多还原