广西地区基因1型丙型肝炎患者NS5A抑制剂天然耐药突变的研究  

Study on natural drug resistance mutations to NS5A inhibitors in patients with genotype 1 hepatitis C virus in Guangxi

作　　者：伍菲菲[1,2] 苏明华 江建宁[1] 阳光 Wu Feifei;Su Minghua;Jiang Jianning;Yang Guang(Department of Infection Diseases,The First Affiliated Hospital of Guangxi Medical University,Nanning530021,China;Guangxi Key Laboratory of AIDS Prevention and Treatment,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院感染性疾病科,南宁530021 [2]广西艾滋病防治研究重点实验室,南宁530021

出　　处：《广西医科大学学报》2018年第4期472-475,共4页Journal of Guangxi Medical University

基　　金：广西壮族自治区教育厅基金资助项目(No.YB2014064);广西壮族自治区卫生厅基金资助项目(No.Z2011346);广西壮族自治区南宁市青秀区科技局基金资助项目(No.2013ZH02)

摘　　要：目的:探讨广西地区未进行抗病毒治疗的基因1型丙型肝炎患者对NS5A抑制剂的天然耐药突变情况。方法:收集2013年5月至2017年11月在广西医科大学第一附属医院感染性疾病科门诊就诊的基因1型丙型肝炎患者134例。提取患者的HCV RNA,设计针对NS5A区域的特异性引物进行巢式PCR扩增,PCR产物经纯化后测序,进行序列比对和耐药分析。结果:134例样本中有119例(基因1a型19例,基因1b型100例)扩增成功,其中53例(44.5%)存在天然耐药位点突变。基因1a型NS5A区7例(36.9%)存在耐药突变(Q30H,n=1,5.3%;H58P,n=1,5.3%;M28T+H58P,n=1,5.3%;H58P+E62D,n=4,21.0%)。基因1b型有46例(46.0%)存在天然耐药突变(R30Q,n=23,23.0%;Y93H,n=6,6.0%;Q54H,n=4,4.0%;P58S,n=4,4.0%;Q54H+P58S,n=4,4.0%;L31M+R30Q,n=2,2.0%;Q54H+R30Q,n=2,2.0%)。结论:广西地区未接受抗病毒治疗的基因1型丙型肝炎患者中有部分患者存在针对NS5A抑制剂的天然耐药位点突变,其突变有单位点突变也有联合位点突变。Objective:To analyze NS5A inhibitor-associated drug resistance mutations in patients with genotype 1 hepatitis C virus without antiviral therapy.Methods:HCV RNA were obtained from 134 patients with genotype 1 hepatitis C virus in our hospital from May 2013 to November 2017.Nested PCR was carried out by designing specific primers for the related drug resistance sites of NS5A region.The PCR products were purified and sequenced,sequence alignment and resistance analysis were performed.Results:A total of 119 cases(there were 19 cases of genotype 1a and 100 cases of genotype 1b)were successfully amplified,of which 44.5%were detected mutation sites.The mutation rate of genotype 1a patients was 36.8%(Q30H,n=1,5.3%;H58P,n=1,5.3%;M28T+H58P,n=1,5.3%;H58P+E62D,n=4,21.0%);the mutation rate of genotype 1b was 46.0%(R30Q,n=23,23.0%;Y93H,n=6,6.0%;Q54H,n=4,4.0%;P58S,n=4,4.0%;Q54H+P58S,n=4,4.0%;L31M+R30Q,n=2,2.0%;Q54H+R30Q,n=2,2.0%).Conclusion:Naturally resistant mutations in NS5A inhibitors existed in some untreated patients with genotype 1 hepatitis C virus in Guangxi.There were single-site mutations and joint site mutations.

关 键 词：丙型肝炎 NS5A抑制剂 耐药突变 

分 类 号：R512.63[医药卫生—内科学]