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Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation

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Abstract

Liver transplantation is one of the most important therapies for end-stage liver diseases and is associated with major problems including infections and acute rejection. The outcome of transplantation can be determined by immune responses as a key role in response to the graft. Inflammatory and anti-inflammatory mediators especially cytokines influence the graft microenvironment. Th1 and Th2 immune responses in contrast to regulatory responses cause acute rejection or help graft survival. In this study, we evaluated the gene polymorphisms of IL-6 G-174C, TGF-β T + 869C, IL-4 C-590T, and IFN-γ T + 874A cytokines in liver transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C, TGF-β T + 869C and IFN-γ T + 874A polymorphisms and PCR-RFLP using AvaII restriction enzyme was done for IL-4 C-590T characterization in 70 liver transplant patients. Acute rejection episodes were diagnosed according to standard criteria. The analysis of the results showed that IL-6-174 GG genotype ( P = 0.009, OR = 4.333, 95% CI = 1.043–18.000), IL-6-174G allele (P = 0.011, OR = 5.273, 95% CI = 1.454–19.127) was more frequent and IFN-γ +874 TT genotype was less frequent (P = 0.043, OR = 0.143, 95% CI = 0.0118–1.190) in acute rejection than in non-rejection patients. TGF-β T + 869C and IL-4 C-590T frequencies were not significantly different (P > 0.05). According to the results, it can be conclude that IL-6 G-174C and IFN-γ T + 874A gene polymorphisms have predictive values for acute rejection after liver transplantation. High producer genotype of IL-6 is a genetic risk factor and IFN-γ is a protective factor for acute rejection development.

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Acknowledgments

This work was supported by a grant from Transplant Research Center of Shiraz University of Medical Sciences. The authors also thank Tarbiat Modares University for their support.

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Authors and Affiliations

  1. Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Saeed Daneshmandi & Ali Akbar Pourfathollah

  2. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Hossein Karimi, Bita Geramizadeh & Ramin Yaghobi

  3. Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Ali Malekhosseini & Saman Nikeghbalian

  4. Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Shahram Bolandparvaz

Authors
  1. Mohammad Hossein Karimi
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  2. Saeed Daneshmandi
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Correspondence to Ali Akbar Pourfathollah.

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Karimi, M.H., Daneshmandi, S., Pourfathollah, A.A. et al. Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation. Mol Biol Rep 38, 4437–4443 (2011). https://doi.org/10.1007/s11033-010-0572-6

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  • DOI: https://doi.org/10.1007/s11033-010-0572-6

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