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Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C

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Abstract

Host genetic variation may affect the outcome of chronic viral hepatitides, favoring viral clearance and/or modulating the inflammatory response to persistent infection. Our aims were to assess whether interleukin 6 (IL-6) promoter polymorphisms are associated with chronic hepatitis C virus (HCV) infection and to clarify the role of IL-6 haplotypes in facilitating progressive disease. The study included 424 Italian patients (233 males, median age 53 years) affected by HCV chronic infection. IL6 −1363, −597, −572, −174, and +2954 polymorphic loci were assayed by means of restriction fragment length polymorphism. Three hundred forty-four healthy Italian blood donors (245 males, median age 50 years) served as controls. Comparing patients and controls analysis of molecular variance was highly significant (p < 0.0001); at a locus by locus approach, the frequencies of minor alleles in the −1363 (p < 0.02), −597 (p < 0.02), and −174 (p < 0.01) polymorphisms were confirmed to be less represented in patients than in controls. Carrying the wild-type G allele at the −597 and −174 loci identified an unfavorable haplotype; carrying the minor allele in one/both loci identified an indifferent/favorable haplotype. Male patients carrying two unfavorable haplotypes had the highest adjusted mean ± standard error Ishak staging score (3.56 ± 0.19), while females carrying one or no unfavorable haplotypes had the lowest (2.69 ± 0.21); the remaining patients had an intermediate value (3.12 ± 0.13, p < 0.01). In conclusion, IL-6 promoter polymorphisms influence the development of chronic HCV infection. With the permissive effect of male gender, haplotypes represented by the wild-type allele for −597 and −174 loci appear to favor a worse evolution of the disease.

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Abbreviations

−1363:

−1363 G>T

−597:

−597 G>A

−572:

−572 G>C

−174:

−174 G>C

+2954:

+2954 G>C

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Acknowledgments

This study is supported in part by grants from the “Ricerca Sanitaria Finalizzata” Program, Regione Piemonte, Italy and Fondazione CRUP Udine, Italy

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Authors and Affiliations

  1. Laboratory Medicine, University of Udine, Udine, Italy

    Annarosa Cussigh, Edmondo Falleti, Sara Cmet & Elisabetta Fontanini

  2. Medical Sciences Clinical and Experimental, Medical Liver Transplant Unit, University of Udine, Udine, Italy

    Carlo Fabris, Davide Bitetto, Sara Bignulin, Ezio Fornasiere, Elisa Fumolo & Pierluigi Toniutto

  3. Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

    Rosalba Minisini & Mario Pirisi

  4. Internal Medicine, Medical Liver Transplant Unit, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy

    Pierluigi Toniutto

Authors
  1. Annarosa Cussigh
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  2. Edmondo Falleti
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  3. Carlo Fabris
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  4. Davide Bitetto
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  5. Sara Cmet
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  6. Elisabetta Fontanini
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  7. Sara Bignulin
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  8. Ezio Fornasiere
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  9. Elisa Fumolo
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  10. Rosalba Minisini
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  11. Mario Pirisi
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  12. Pierluigi Toniutto
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Correspondence to Pierluigi Toniutto.

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Cussigh, A., Falleti, E., Fabris, C. et al. Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 63, 33–41 (2011). https://doi.org/10.1007/s00251-010-0491-7

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  • DOI: https://doi.org/10.1007/s00251-010-0491-7

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