Association of TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism with acute rejection and infection in lung transplant recipients

Clin Transplant. 2014 Sep;28(9):1016-24. doi: 10.1111/ctr.12411. Epub 2014 Jul 24.

Abstract

Infection and rejection are common complications faced by lung transplant recipients (LTRs) and have become major impediments to long-term survival. Cytokines may play an important role in the development of these complications. In this study, we explored the correlation between TNF-α (-308 A/G), TGF-β1 (+869 T/C, +915 G/C), IL-10 (-592 C/A, -819 T/C, -1082 G/A), IL-6 (-174 G/C), and IFN-γ (+874 T/A) gene polymorphisms and the incidence of acute rejection and infection. Transplant outcomes were reviewed in a retrospective cohort of 113 LTRs from a single center between December 2004 and November 2012. Cytokine polymorphisms were measured using sequence-specific primer-based PCR. HLA typing was performed for the donors and recipients. We found that the LTRs with the IL-10 -819 CC and -592 CC genotypes had a significantly decreased risk of infection (p = 0.017, OR = 0.177, 95% CI = 0.04-0.85). However, we found no significant association between cytokine polymorphisms and acute rejection. Furthermore, the data revealed that the occurrence of acute rejection was strongly associated with infection episodes (χ(2) = 8.5256, p < 0.01). These results suggest that LTRs possessing the IL-10 -819 CC and -592 CC genotype may be protected from the occurrence of infection. Our results demonstrated that infection is an important cause of acute rejection for LTRs.

Keywords: cytokine; infection; lung transplant; rejection; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • Cytokines / genetics*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / genetics*
  • Graft Rejection / prevention & control
  • Graft Survival
  • Histocompatibility Testing
  • Humans
  • Infections / genetics*
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-6 / genetics
  • Lung Diseases / genetics*
  • Lung Diseases / surgery
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Transforming Growth Factor beta1 / genetics
  • Transplant Recipients
  • Tumor Necrosis Factor-alpha / genetics
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma