Genetic Polymorphism of Interferon-γ, Interferon-γ Receptor, and Interferon Regulatory Factor-1 Genes in Patients with Hepatitis B Virus Infection

Abstract

The natural history of hepatitis B virus (HBV) infection is probably related to host immune factors. Interferon-c (IFN-c) plays significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of IFN-c, IFN-c receptor (IFNGR)-1 and 2, and interferon regulatory factor (IRF)-1 genes. Between March 2002 and December 2002, 614 Korean patients were enrolled in two different groups: an HBV clearance group (n = 201), who were hepatitis B surface antigen (HBsAg) negative with antibodies to HBsAg and hepatitis B core antigen, and an HBV persistence group (n = 413), who were repeatedly HBsAg positive. We assessed polymorphisms in the IFN-c gene at position +874, in the IFNGR-1 gene at positions )56 and +95, in the IFNGR-2 gene at the second position of codon 64 (Gln64Arg), and in the IRF-1 gene promoter ()410, )388), and the genotype distributions of the HBV clearance and persistence groups were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-c,

Association of Interleukin-18 Gene Polymorphisms with Hepatitis B Virus Clearance

“…Previous reports have shown that several cytokine polymorphisms are associated with the natural history of HBV infection in Korea [22,23]. Recently, we demonstrated associations between IFN-c-related gene SNPs and HBV clearance [13]. Cytotoxic T lymphocytes may damage HBV-infected hepatocytes by releasing humoral immune mediators of inflammation such as IL-2, tumor necrosis factor (TNF)-a, and IFN-c [24].…”

“…We have previously demonstrated some of the host genetic factors that are associated with HBV infection outcome in the Korean population [11][12][13]. IL-18 plays a pivotal role in inducing cytotoxic T lymphocyte response, which is important in the outcome of HBV infection; for this reason, we analyzed IL-18 single-nucleotide polymorphisms (SNPs) as potential candidates for HBV-clearance agents.…”

A Functional SNP of the Interleukin-18 Gene Is Associated with the Presence of Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients

“…Shin et al [10] reported that IL10-ht2 (high IL-10 secretor phenotype) accelerates the progression of chronic HBV infection, especially the development of HCC in the Korean population, although the exact functional mechanisms of HCC occurrence were not clearly explained. Recently, we demonstrated an association between IFN-c-related gene SNPs and HBV outcome [13]. Cytotoxic T lymphocytes [24].…”

“…Our research group has investigated host genetic factors that are associated with HBV infection outcomes [11][12][13]. As part of our effort to identify additional SNPs in genes implicated in the outcome of HBV infection, we analyzed IL-18 SNPs as potential candidates for the development of HCC in HBVinfected individuals, and the biological relevance of the significantly associated SNP was assessed by a functional study in vitro.…”

Identification of the transcriptional regulators by expression profiling infected with hepatitis B virus

“…IRF1 has been shown to play roles in regulating apoptosis, tumor-suppression and DNA damage response [71,72]. Findings suggest that IRF1 is a candidate gene marker for determining patient susceptibility to the development of chronic hepatitis B and C [73,74]. Some findings indicate that a common mis-sense SNP in ATF6 may contribute to susceptibility of HCC functionally [75].…”