Abstract
Background and AimsInterferon-gamma induced protein 10 (IP-10) was suggested to be involved in liver injury in viral hepatitis. This study aimed to investigate the impact of the single nucleotide polymorphisms (SNP) G-201A (rs1439490) in IP-10 gene on disease progression of hepatitis B virus (HBV) infection.MethodsThe -201 SNP in IP-10 promoter was genotyped from 577 patients with different illness categories and 275 health controls; In vitro IP-10 promoter activity was compared between haplotype GG and AA homozygotes using luciferase reporter system in HepG2 cells. In vivo expression of IP-10 was compared between patients with -201 AA genotype and GG genotype.ResultsThe detected frequency of G-201A SNP was 17.8%, 25.3%, 26.6%, and 13.8% for patients with acute hepatitis B (AHB), patients with mild chronic hepatitis B (CHB-M), patients with severe chronic hepatitis B (CHB-S), and health controls, respectively. In vitro IP-10 promoter-driven luciferase activity in pGL3-Enhancer-201A transfected HepG2 cells was 1.43-fold higher than that in pGL3-Enhancer-201G transfected HepG2 cells (P<0.01). In vivo IP-10 transcriptional expression of peripheral blood mononuclear cells was 1.38-fold higher in patients with -201 AA genotype than in patients with -201 GG genotype (P<0.01).ConclusionG-201A in promoter region of IP-10 gene was associated with liver disease progression in patients with HBV infection through up-regulating IP-10 expression.
Highlights
Hepatitis B virus (HBV) is non-cytopathic itself and the liver damage caused by hepatitis B virus (HBV) infection is mainly immune-mediated [1]
Genetic susceptibilities such as some single nucleotide polymorphisms (SNPs) in human genes have been reported to be associated with viral clearance in HBV infection [2,3,4]
For the test consistence of SNP detection method, PCR-RFLP method showed a 98.7% identity with the results from direct PCR sequencing by Kappa test and indicated that the two methods were statistical consistent (P,0 .05)
Summary
Hepatitis B virus (HBV) is non-cytopathic itself and the liver damage caused by HBV infection is mainly immune-mediated [1]. The clinical resolution and disease progression of HBV infection are subsequent to the interaction between host immune responses and viral factors. Genetic susceptibilities such as some single nucleotide polymorphisms (SNPs) in human genes have been reported to be associated with viral clearance in HBV infection [2,3,4]. This study aimed to investigate the impact of the single nucleotide polymorphisms (SNP) G-201A (rs1439490) in IP-10 gene on disease progression of hepatitis B virus (HBV) infection
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