Analysis of Human Adaptor Protein Gene in Hepatitis C Virus Infection

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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.