丙型肝炎病毒1b型NS5A基因变异与干扰素疗效关系研究  

Association between NS5A Gene Sequence and Response to Interferon Therapy in Chronic Hepatitis C Patients

作　　者：周朝晖[1] 佘为民 钱雪梅[2] 全彩娟[2] 

机构地区：[1]复旦大学附属中山医院消化科,上海200032 [2]复旦大学附属中山医院青浦分院感染科,上海201700

出　　处：《中国临床医学》2008年第6期802-804,共3页Chinese Journal of Clinical Medicine

摘　　要：目的:探讨上海地区丙型肝炎病毒(HCV)1b亚型慢性感染者的血清HCV非结构基因5A(NS5A)与干扰素(IFN)疗效的关系。方法:收集上海地区32例HCV1b亚型慢性感染者在干扰素治疗前后及随访过程中的血清标本,定量检测治疗血清HCV RNA,用逆转录-集合酶链反应方法扩增NS5A的干扰素敏感决定区(ISDR)基因并进行测序和分析。结果:治疗前血清HCV RNA的定量结果显示,持续应答组的病毒滴度(平均滴度4.50×104拷贝数.mL-1)明显低于复发组和无应答组(平均滴度1.82×107拷贝数.mL-1)。32例慢性丙型肝炎干扰素治疗前血清HCV的ISDR氨基酸序列与抗干扰素的HCV-J株比较,22例为野生型,10例为中间型,无突变型。12例完全应答者8例感染的是野生型株,4例感染的是中间型病毒株。5株HCV病毒的NS5A全长序列种系发生树显示,3种不同应答类型株在种系发生上分属3个组别,无应答株与抗干扰素的HCV-J株关系相近被归为1组。蛋白质二级结构预测显示,上述病毒株NSSA蛋白在二级结构方面基本相似,仅在2255—2289范围内有明显不同,这一区域与PKR结合域部分重叠。结论:HCVNS5A基因的ISDR区不能单独用于预测干扰素疗效,治疗前血清HCV RNA水平结合NS5A区的PKR结合域序列的分析,可能有助于预测干扰素疗效,指导临床用药。Objective：To elucidate relationship between amino acid sequence of non structural protein 5A（NS5A） of HCV （1 b） and outcome patients with chronic hepatitis C after interferon （IFNα） therapy. Methods： Sera of 32 patients were collected before, during and after IFNα therapy. Pretreatment RNA levels and the sequences of HCV NS5A interferon sensitivity determining region （ISDR） were determined. Results： Pretreatment RNA levels of sustained response group were significantly lowere than that of non response group and relapse group （4.50 × 10^4 copies/ml versus 1.82 × 10^7 copies/ml, P（0.01 ）. ISDR sequences of NS5A from pretreatment sera were compared with HCV-J strain （prototype）. Thirteen of 24 isolates were wild type, 11 of 24 were intermediate type and none of them was mutant type. 3 of 6 sustained responders were infected with wildtype isolates, the rest with intermediate type isolates. Phylogenetic tree based on NS5A full-length sequences classified 5 isolates with 3 different response types into 3 groups. NON response isolates belonged to the same group as HCV-J. Secondary structure prediction of 5 isolates revealed significant differences existing in 2 255-2 289. This region was partly overlapped with PKR-binding domain. Conclusion：Low HCV RNA levels in serum are associated with favorable outcome of IFNα therapy. ISDR sequence alone could not predict outcome of IFN treatment. Combination of determination of HCV RNA levels in serum with sequence analysis of PKR binding domain may he helpful in predicting the efficacy of IFN therapy.

关 键 词：丙型肝炎 基因变异 干扰素 

分 类 号：R512.63[医药卫生—内科学]