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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 relationship between the amino acid sequence variation of Peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) antiviral therapy in patients with genotype 1b chronic hepatitis C (CHC). Methods Nineteen patients with genotype 1b CHC treated with PegIFNα-2a / RBV antiviral therapy for 48 weeks were given fast response and nine patients were nonresponders. The full-length HCV genome sequence was amplified by RT-PCR and the nucleotide sequence was determined by cloning and sequencing. The differences between the two sequences were compared at the amino acid level. As a result, no single amino acid variation associated with treatment response was found, and phylogenetic analysis did not show a clustering of mutations associated with the response. Further comparison showed that the number of amino acid mutations (aa 371-458) and NS5A-V3 (aa 384-407) in the NS5B region, especially in the part of the thumb area, correlated with the PegIFNα-2a anti-RBV antiviral response (P <0.01 And P <0.05). There was a positive correlation between the number of amino acid mutations in NS5B region and the number of amino acid mutations in V3 region (r = 0.568, P <0.05). Conclusion The number of amino acid mutations in the NS5B region, especially in some thumb regions, and the number of amino acid mutations in V3 region may be related to the efficacy of interferon.