Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation

Transplantation. 2001 Mar 15;71(5):674-7. doi: 10.1097/00007890-200103150-00018.

Abstract

Background: Our group has previously described five different size alleles of an interferon (IFN)-gamma microsatellite. Analyzing this polymorphism, this study correlated high IFN-gamma production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status.

Methods: Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-gamma and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups.

Results: The genotype associated with high IFN-gamma production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-gamma genotype group, compared with 44.4% in the low IFN-gamma group. Requirement for antithymocyte globulin therapy was greater in the high IFN-gamma group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-gamma genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-gamma genotype had a 61% incidence of rejection compared with only 20% in the low IFN-gamma genotype patients (OR=3.06). Graft survival was similar between the two groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-gamma genotype patients had serum creatinine levels above 200 micromol/L compared with only 14.3% of the low IFN-gamma genotype recipients at 5 years after transplantation (P=0.05). The high IL-10 genotype was shown to be associated with better graft function at 5 years (75 vs. 50%, P=0.09).

Conclusion: In this study we have shown that high producer genotype for IFN-gamma may have an influence on acute rejection of kidney transplants, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.

MeSH terms

  • Acute Disease
  • Adult
  • Alleles
  • Cytokines / genetics
  • Gene Frequency
  • Genotype
  • Graft Rejection / epidemiology
  • Graft Rejection / genetics
  • Graft Rejection / therapy
  • HLA-DR Antigens / analysis
  • Histocompatibility Testing
  • Humans
  • Immunosuppression
  • Incidence
  • Interferon-gamma / genetics*
  • Interleukin-10 / genetics*
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Polymorphism, Genetic*
  • Reference Values
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Cytokines
  • HLA-DR Antigens
  • Interleukin-10
  • Interferon-gamma