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Gene Polymorphisms of IL-10 and MxA in Responders and Non-responders to Interferon Therapy in HCV Egyptian Patients Genotype 4

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Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. The standard regimen for treatment of HCV consists of a combination of pegylated interferon with ribavirin. Failure of interferon-α treatment in patients with chronic HCV infection remains a challenging obstacle. Both viral and host environmental factors have been implicated in reducing responsiveness to IFN-α therapy. Host genetic diversity is also believed to contribute to the different clinical outcomes in HCV infection. The objective of the study was to investigate the association of both IL-10 (−819 and −592) and MxA (−88 and −123) single-nucleotide polymorphisms (SNPs) of the promoter regions, with response to interferon (IFN) therapy in Egyptian patients infected with HCV genotype 4. Polymorphisms of both genes in 85 HCV patients and 100 controls were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique. The frequency of SNP was compared between sustained responders (n = 52) and non-responders (n = 33), as determined by biochemical and virological response to IFN and ribavirin combined therapy. The frequency of the −819T/T and the −592A/A genotypes of IL-10 was significantly higher among responders compared to non-responders (51.92 vs 39.4 %, P = 0.03; 51.92 vs 42.42 %;P = 0.046 respectively). The G/G genotype at position −88 of the MxA gene was significantly lower in responders than in non-responders (25 vs 75.76 %, P = 0.046), whereas heterozygotes (G/T) were more likely responders (65.38 vs 18.18 %, P = 0). The −123C/A genotype was significantly associated with responders (48.08 vs 30.30 %, P = 0.014). Findings suggest that homozygosity for both −819T/T and −592A/A polymorphisms of IL-10 gene and that heterozygosity for both −88G/T and −123C/A polymorphisms of the MxA gene are important host factors that influence the response to IFN therapy in patients with chronic HCV infection.

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Abbreviations

ALT:

Alanine aminotransferase

CTL:

Cytotoxic T lymphocytes

HCV:

Hepatitis C virus

IFN:

Interferon

IL:

Interleukin

ISRE:

Interferon-stimulated response elements

MxA:

Myxovirus resistance A

NR:

Non-responders

OAS:

Oligoadenylate synthetase

PCR:

Polymerase chain reaction

PEG:

Pegylated

PKR:

dsRNA-activated protein kinase

RFLP:

Restriction fragment length polymorphism

STAT:

Signal transducer and activator of transcription

SNP:

Single-nucleotide polymorphism

SOC:

Standard of care

SOCS:

Suppressor of cytokine signaling

SR:

Sustained responders

SVR:

Sustained virological response

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Acknowledgments

This work was supported by the Egyptian Science and Technology Development Fund [Project Number 1512 to PI; Olfat Shaker]. The author(s) received no financial support for the research and/or authorship of this article.

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt

    Olfat G. Shaker

  2. Biochemistry Department, Faculty of Pharmacy, Cairo University, Giza, Egypt

    Mohamed T. Abdel-Rahim

  3. Egyptian Company for Production of Biological Products and Vaccines and Sera-EGYVAC, Giza, Egypt

    Salma T. Bayoumi

Authors
  1. Olfat G. Shaker
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  2. Mohamed T. Abdel-Rahim
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  3. Salma T. Bayoumi
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Correspondence to Olfat G. Shaker.

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Olfat G. Shaker, Mohamed T. Abdel-Rahim, Salma T. Bayoumi have contributed to the work; all authors have agreed to submit the manuscript for publication , and all human studies have been reviewed by the appropriate ethics committees.

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Shaker, O.G., Abdel-Rahim, M.T. & Bayoumi, S.T. Gene Polymorphisms of IL-10 and MxA in Responders and Non-responders to Interferon Therapy in HCV Egyptian Patients Genotype 4. Cell Biochem Biophys 71, 617–625 (2015). https://doi.org/10.1007/s12013-014-0241-9

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  • DOI: https://doi.org/10.1007/s12013-014-0241-9

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