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IL-18 AND IFN-γ GENOTYPE CORRELATION WITH ALLOGRAFT FUNCTION IN AFRICAN-AMERICAN RENAL TRANSPLANT PATIENTS.
Xinchun Zhou M.D. , Henry Barber M.D. , Donald E. Butkus, M.D. , Larry S. McDaniel, Ph.D. , Brenda Mangilog M.S. and Olga McDaniel Ph.D. . Jackson MS, USA, University of MS Medical Center, 39216, Surgery ; Jackson MS, USA, University of MS Medical Center, 39216, Medicine and Jackson MS, USA, University of MS Medical Center, 39216, Microbiology .
It was hypothesized that a high producing IFN-γ allele might be influential in predisposing the recipient to allograft rejection and the IL-18 cytokine genotype might play an important role in the induction of IFN-γ . Thus, the purpose of this study is to characterize the IL-18 genotype, in relation to IFN-γ production and the outcome of allograft function in kidney recipients. Cytokine gene polymorphisms were evaluated in 77 African-American patients who had undergone renal transplantation. The frequency distributions of cytokines were analyzed in respect to the clinical characterization, including delayed graft function (DGF), rejection episodes (REs) and stable graft function (SGF). We have shown that the IFN-γ T/A intermediate producer genotype was associated with allograft rejection (69.2%), whereas the IFN-γ A/A low producer genotype was significantly protective of the allograft (23.1% in REs and 65.9% in SGF, p<0.008, RR=2.85). The IL-18 CC/GG high producer and the CA/GC intermediate producer genotypes were found in a higher frequency in recipients with DGF and RE (48%/46% and 38%/46% respectively) as compared with SGF and controls (36%/34% and 18%/25% respectively). Although this difference did not reach statistical significance, it may be of importance, since all 9 (69.2%) recipients in RE group that carry the IFN-γ T/A intermediate genotype also carry either IL-18 CC/GG or CA/GC genotypes. These findings support a role for IL-18 induction of IFN-γ and might provide better understanding of the posttransplantation cytokine release and the management of allograft survival.