Polymorphisms in the interferon-γ gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-α and ribavirin

Dai, Chia‐Yen; Chuang, Wan‐Long; Chang, Wen‐Yu; Chen, Shinn‐Cherng; Lee, Li‐Po; Hsieh, Ming‐Yen; Hou, Nai‐Jen; Hsieh, Ming‐Yuh; Wang, Liang‐Yen; Yu, Ming‐Lung

doi:10.1016/j.antiviral.2005.04.003

Cited by 20 publications

(13 citation statements)

References 32 publications

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“…The relationship between several IFN-␥ gene polymorphism and outcomes of HCV infection has been studied previously. One paper reported the correlation of the ϩ874T/A polymorphism with early recurrent hepatitis C after liver transplantation (22), but many other groups did not demonstrate any association with either viral clearance or treatment response (23)(24)(25)(26). Although our study did not demonstrate a significant association of the ϩ874T/A SNP (rs2430561), we did identify the SNP variant Ϫ764G of the IFN-␥ gene as an independent marker predicting SVR to IFN-␣-based therapy.…”

Section: Discussioncontrasting

confidence: 53%

A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection

Huang

Yang

Borg

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

106

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Cytokine polymorphisms are associated with disease outcome and interferon (IFN) treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs spanning the entire IFN-γ gene in two cohorts and assessed the association between those polymorphisms and treatment response or spontaneous viral clearance. The first cohort was composed of 284 chronically HCV-infected patients who had received IFN-α-based therapy and the second was 251 i.v. drug users who had either spontaneously cleared HCV or become chronically infected. A SNP variant located in the proximal IFN-γ promoter region next to the binding motif of heat shock transcription factor (HSF), −764G, was significantly associated with sustained virological response [ P = 0.04, odds ratio (OR) = 3.51 (confidence interval 1.0–12.5)]. The association was independently significant in multiple logistic regression ( P = 0.04) along with race, viral titer, and genotype. This variant was also significantly associated with spontaneous recovery [ P = 0.04, OR = 3.51 (1.0–12.5)] in the second cohort. Functional analyses show that the G allele confers a two- to three-fold higher promoter activity and stronger binding affinity to HSF1 than the C allele. Our study suggests that the IFN-γ promoter SNP −764G/C is functionally important in determining viral clearance and treatment response in HCV-infected patients and may be used as a genetic marker to predict sustained virological response in HCV-infected patients.

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Section: Discussioncontrasting

confidence: 53%

A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection

Huang

Yang

Borg

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

106

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“…IFN-␥ is similarly important for virus control in HCV [58] , while the role of perforins in human hepatitis is elusive at present.…”

Section: Langmentioning

confidence: 99%

Host Mechanisms in Viral Hepatitis

Lang

2010

Dig Dis

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Hepatitis, a common human disease, may be followed by severe liver injury, eventually leading to fatty liver, liver fibrosis and hepatocellular carcinoma. CD8 T cells are a double-edged sword in the response to infection with the hepatitis virus. On one hand, rapid activation of CD8 T cells is critically important for the elimination of the virus. On the other hand, in persistent viral infection, the activation of CD8 T cells substantially contributes to liver injury. The clinical course of hepatitis, thus, critically depends on mechanisms regulating the activity of CD8 T cells. In observations in human hepatitis and in mice infected with the lymphocytic choriomeningitis virus, the clinical course of hepatitis is modified by several immunological factors including neutralizing antibodies: RIG-I, TLRs, MyD88, interferon type I, TNF-α, MHC I, Tap, TCR, CD8, IL-2, IL-7, PD-1, IFN-I, IL-10, IFN-γ, perforins, serotonin and iNOS (table 1) . Additional experimental effort is needed to understand the concerted interplay of those molecules in viral hepatitis of man and mice.

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“…Vários estudos têm demonstrado a influência de fatores genéticos na infecção causada pelo VHC (Aguilar-Reina et al, 2005;Barrett et al, 2003;Dai et al, 2005;Dai et al, 2006;Edwards-Smith, 1999;Huang et al, 2007;Lio et al, 2003;Minton et al, 2005;Paladino et al, 2006;Persico et al, 2006, Thio et al, 2000Saito et al, 2004;Suzuki et al, 2004;Valenti et al, 2005;Yee et al, 2001). …”

Section: Os Resultados De Estudos De Doenças Autoimunes E Infecciosasunclassified

“…Diversos polimorfismos nos genes das citocinas IL1, IL6, TGF-, Interferon-γ foram estudados em diversas populações, contudo, com resultados discordantes (Barrett et al, 2003;Dai et al, 2005;Huang et al, 2007;Minton et al, 2005;Paladino et al, 2006;Thio et al, 2000;Saito et al, 2004).…”

Section: Os Resultados De Estudos De Doenças Autoimunes E Infecciosasunclassified

“…Porém, diversos estudos realizados com diferentes populações apresentaram resultados conflitantes, mostrando forte associação com a resposta ao tratamento antiviral em alguns, e pouco ou nenhuma associação em outras, mostrando claramente o efeito da heterogeneidade genética das populações de estudo (Barrett et al, 2003;Dai et al, 2005;Dai et al, 2006;Edwards-Smith, 1999;Lio et al, 2003;Minton et al, 2005;Paladino et al, 2006;Persico et al, 2006, Thio et al, 2000Valenti et al, 2005;Yee et al, 2001). …”

Section: Snps Encontrados Nos Genes Do Fator De Necrose Tumoral-(tnf-α)unclassified

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Influência dos polimorfismos no promotor do gene da interleucina-10 na resposta a antivirais em pacientes com hepatite C crônica

Melo¹

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Polymorphisms in the interferon-γ gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-α and ribavirin

Cited by 20 publications

References 32 publications

A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection

A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection

Host Mechanisms in Viral Hepatitis

Influência dos polimorfismos no promotor do gene da interleucina-10 na resposta a antivirais em pacientes com hepatite C crônica

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