丙型肝炎病毒1b型NS3区与原发性肝癌的关系

Correlation between nonstructural protein 3 of chronic genotype 1b hepatitis C virus and development of hepatocellular carcinoma

目的:探讨丙型肝炎病毒(HCV)1b型的非结构蛋白3(NS3)区与原发性肝癌(HCC)的关系。方法:将患者分为丙型肝炎病毒携带者组、非HCC组及HCC组,从患者血清中提取HCV-RNA,采用巢式聚合酶链法(nested-PCR)进行HCV基因分型并扩增HCV-NS3片段,分析HCV-NS3区片段的核苷酸序列、氨基酸序列、蛋白质二级结构。结果:3组均以1b型为主,3组间1b型所占百分率比较差异无显著性(P>0.05);3组核苷酸序列同源性95%,3组氨基酸序列的同源性为95%,且3组在NS31027-1206区间都无特殊的氨基酸突变;NS31027-1206区的蛋白质二级结构分为A、B 2型,携带组及非HCC组以A型为主,而HCC组以B型为主;携带组与非HCC组蛋白质二级结构分型差异无显著性(P>0.05),而HCC组与携带组、非HCC组之间差异有显著性(P<0.01)。结论:1b型HCV携带者及非HCC患者与HCC患者在蛋白质二级结构上有差异,HCV-NS3与HCC的发生有关联。

Objective To investigate the correlation between the nonstructural protein 3 （NS3） of chronic genotype lb hepatitis C virus （HCV） and development of hepatocellular carcinoma （HCC）. Methods The sera were collected from HCV-carriers and HCV-infected Chinese patients with and without HCC, HCV-RNA extracted from these serum samples were amplified by nested polymerase chain reaction （nested-PCR） to obtain the genotype 1b and NS3 region PCR products, GENETYX-Mac ver 10.1 software was used to analysis the nucleotide sequence, amino acid sequence and the secondary structure of NS31027- 1206. Results The genotype lb became predominant in all the patients, and the percentage had no statistically significant difference （P〉0.05）. The homology of nucleotide and amino acid sequence was 95%, there was no particular mutation in the NS31027-1206 region amino acid sequence. On the basis of secondary structure of NS31027-1206 , the HCV isolates were classified into two types： type A and type B;type A was predominant in the carriers and non-HCC patients, type B was predominant in the HCC patients. The difference in the distribution pattern of those types between carriers and non-HCC patients was no statistically significant （P〉0.05）, but was statistically significant （P〈0. 01） between carriers, non-HCC patients and HCC patients. Conclusion There is difference in the secondary structure of NS31027- 1206 of carriers, non-HCC and HCC patients, and HCV-NS3 has correlation with the development of HCC.