Analysis of Human Adaptor Protein Gene in Hepatitis C Virus Infection

丙型肝炎病毒感染中的人衔接蛋白基因分析

• 批准号: 17590611
• 负责人: SAITO Takafumi
• 金额: $ 2.24万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590611/
• 关键词: Hepatitis C; host; genetic polymorphism; SNP; susceptibility of infection; cell membrane; cohort; glycosylation; 感染感受性; 遺伝子多型; 接合蛋白; ヘパラン硫酸; HCV; 感染防御

The outcome of hepatitis C virus (HCV) infection varies among individuals, but the genetic factors involved remain unknown. We have reported the 50 SNPs in 32 genes as candidate genes that influence the susceptibility of infection (BBRC 2004 ; 317 : 335-341). From these candidate genes, we further analyzed the genes coding the adaptor proteins that are essential for viral attachment onto cell surface. The HCV virion has been reported to bind heparan sulfate proteoglycan (HS) on the cell surface in the initial step of infection. In this study, we determined the genetic polymorphisms in NDST3 gene that influence the sulfotransferation of HS, and also found the haplotype of this gene. These genetic variations were closely associated with the natural clearance of HCV in the host. We further analyzed the SNPs of the surrounding genes of genes coding the adaptor proteins, and we determined the genetic polymorphisms of TM7SF2 gene in relation to the natural clearance of HCV. The product of TM7SF2 gene is essential for cholesterol synthesis in the liver. This polymorphism represented a coding SNP. Using siRNA technique, we clarified the suppression of HCV replication in the cells after TM7SF2-siRNA transfection in vitro. Thus the genetic variation of TM7SF2 was shown as an important polymorphism that is linked to replication of HCV in the host.

丙型肝炎病毒(丙型肝炎病毒)感染的结局因人而异，但涉及的遗传因素尚不清楚。我们已经报道了32个基因中的50个SNPs作为影响感染易感性的候选基因(BBRC2004；317：335-341)。从这些候选基因中，我们进一步分析了编码适配蛋白的基因，这些适配蛋白是病毒附着到细胞表面所必需的。据报道，在感染的最初阶段，丙型肝炎病毒粒子与细胞表面的硫酸乙酰肝素蛋白多糖(HS)结合。在本研究中，我们检测了影响HS硫代转移的NDST3基因的遗传多态性，并发现了该基因的单倍型。这些基因变异与丙型肝炎病毒在宿主体内的自然清除密切相关。我们进一步分析了编码适配蛋白的基因周围基因的SNPs，并确定了TM7SF2基因的遗传多态与丙型肝炎病毒自然清除的关系。TM7SF2基因产物是肝脏合成胆固醇所必需的。这种多态代表了编码的SNP。利用siRNA技术，明确了TM7SF2-siRNA在体外对细胞内丙型肝炎病毒复制的抑制作用。因此，TM7SF2的遗传变异被认为是与丙型肝炎病毒在宿主体内复制有关的一个重要的多态性。

项目成果

Saito T, et al. Association of transforming growth factor (TGF)-beta1 functional polymorphisms with natural clearance of hepatitis C virus

齐藤 T 等人。

• 发表时间: 2006
• 期刊: Journal of Infectious Diseases 193
• 作者: Nagasaki F;Niitsuma H;Cervantes JG;Chiba M;Hong S;Ojima T;Ueno Y;et al.;Kimura T
• 通讯作者: Kimura T

Association of transforming growth factor (TGF) -β1 functional polymorphisms with natural clearance of hepatitis C virus

转化生长因子（TGF）-β1功能多态性与丙型肝炎病毒自然清除的关联

• 发表时间: 2006
• 期刊: Journal of Infectious diseases 193
• 作者: Kimura T;Saito T;et al.
• 通讯作者: et al.

肝検診地域の住民におけるC型肝炎ウイルス感染感受性遺伝子の解析

肝脏筛查地区居民丙型肝炎病毒感染易感基因分析

• 发表时间: 2005
• 期刊: 日本消化器集団検診学会雑誌 43
• 作者: Yuasa K;Naganuma A;Sato K;Ikeda M;Kato N;Takagi H;Mori M;斎藤貴史
• 通讯作者: 斎藤貴史