【作者】 董秋明；

【导师】 高锦声； 卢大儒；

【作者基本信息】 苏州大学 ， 细胞生物学， 2001， 硕士

【摘要】 丙型肝炎（HC）是由丙型肝炎病毒（HCV）引起，可导致肝硬化和肝癌。除了环境因素即不同类型HCV的感染，人群中确实存在着易感性的差异，从而使他们对HCV感染产生不同的效应。HCV感染的机制目前尚不明了，大量的证据表明CD81是该病毒最初感染的受体，结合位点位于CD81的细胞外环EC2上；也有实验认为病毒是与密度脂蛋白结合后通过低密度脂蛋白受体（LDL-R）的介导进入细胞的。非洲绿猴（AGM）的CD81不与HCV结合，而它和人的CD81有四个氨基酸（163，186，188，196）不同，位于EC2环，对应于CD81基因的第6、7外显子。目的 探讨CD81、LDL-R基因在中国人中是否存在与HCV感染有关的单核苷酸多态性（SNP）。方法 利用PCR结合DNA测序的方法，对HCV感染阳性病人和阴性正常人群的CD81的EC2环相对应的第6、7、8外显子以及LDL-R的配体结合结构域所对应的的第2、3、4、5、6外显子的DNA进行检测。结果 （1）在以上四个氨基酸位点所对应的CD81的外显子6、7并没有发现单核苷酸多态性（SNP），外显子8也没有发现SNP；尽管在内含子6（11028G/T）和3′下游调控区（11860C/T，11960G/A）发现了三个多态位点，但它们不影响蛋白质的一级结构，并且与HCV的感染无关（P＞0.05）。（2）LDLR的外显子2、3、4、5、6也不存在SNP；虽然在内含子2发现了3个SNPs，它们也与HCV感染的易感性无关（P＞0.05）。结论 （1）CD81外显子6、7、8与HCV感染的易感性无关，以上四个氨基酸的遗传基础在中国人中是高度保守的；由于CD81蛋白的其它位点在种间是高度保守的， CD81，LDLR单核菩酸多态拄与丙型肝炎病毒感染易感性的相关性研究 摘要 因此，在中国人群中 CDSI蛋白的多态性稀少或不存在。u）HCV感染 的易感性与LDLR的配体结合结构域的遗传基础无关。更多还原

【Abstract】 Hepatitis C (HC) is caused by hepatitis C virus(HCV) ,which could lead to cirrhosis and liver cancers. Except for environment factor, the infection of different types of HCV, there exists difference of genetic susceptibility which can lead to various effects in human population. The mechanism by which HCV infects host cells remains unknown. A great deal of evidence shows that human CD81 is a first receptor of HCV infection by the binding of its extracellular loop EC2 and HCV. Low Density Lipoprotein Receptor (LDLR) is also regarded as a receptor, which conducts HCV into cells after the binding of HCV to density lipoprotein. HCV can not bind the CD81 of African Green Monkey(AGM). Four amino acids(163, 186, 188, 196) locating in EC2 of CD8I are different between human and AGM. Objective The study was conducted to investigate whether there is single nucleotide polymorphism(SNP) which has relation with the infection of HCV in CD81 gene or LDLR gene in Chinese population. Methods PCR and DNA sequencing methods were used to examine exon 6, 7, 8 of CD81 which are the correspondent sites of the EC2 and exon 2,3,4,5,6 of ligand binding region of LDLR in healthy people and patients withmHCV infection. Results (l)No SNP was found in exon 6,7,8 of CD81.Though three SNPs were found in intron 6 (11028G/T)and3downstream regulatory region (11860C/T, 11960G/A), they did not effect the primary structure of CD81 protein and had nothing to do with the susceptibility of HCV infection(P>O.05). (2) Exon 2,3,4,5,6 of LDLR gene also had no SNP, but three SNPs were found in intron 2, which also had no relation with the susceptibility of HCV infection(P>O. 05). Conclusion (1) Exon 6,7,8 have no relation with the susceptibility of HCV infection. The genetic basis of the four amino acids is highly conserved in Chinese population. Because other sites of CD81 protein are highly conserved among species, there is no or very rare polymorphism of CD8I in Chinese people. (2) The susceptibility of HCV infection has nothing to do with the genetic basis of the ligand binding region of LDLR.Postgraduate DongQiumingDirected by Professor Gao JinshengProfessor Lu Daru更多还原