ASSOCIATION OF POLYMORPHISMS IN THE HUMAN INTERFERON -?? AND INTERLEUKIN-10 GENE WITH ACUTE AND CHRONIC KIDNEY TRANSPLANT OUTCOME
| Autor: | Vera Pravica, David Sankaran, Ian Roberts, Paul J. Sinnott, Ian V. Hutchinson, Argiris Asderakis, Robert W. G. Johnson, Phil Dyer |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Graft Rejection Time Factors Genotype Kidney Interferon-gamma chemistry.chemical_compound Gene Frequency Reference Values Polymorphism (computer science) medicine Humans Interferon gamma Alleles Immunosuppression Therapy Transplantation Creatinine Polymorphism Genetic business.industry Histocompatibility Testing Incidence Interleukin HLA-DR Antigens Odds ratio Kidney Transplantation Survival Analysis Interleukin-10 Treatment Outcome medicine.anatomical_structure chemistry Acute Disease Immunology Cytokines business medicine.drug |
| Zdroj: | Transplantation. 71:674-678 |
| ISSN: | 0041-1337 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|