CYTOKINE GENE POLYMORPHISMS AND RENAL TRANSPLANTATION.

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CYTOKINE GENE POLYMORPHISMS AND RENAL TRANSPLANTATION.
Narelle Watson BSc , Andrew Geczy PhD DSc , John Sullivan PhD MPH and Kevin Broady PhD . Sydney New South Wales, Australia, Australian Red Cross Blood Service, 2000, Tissue Typing Services and Sydney NSW, Australia, University of Technology, 2000, Department of Molecular Biology .

This study examined the role of a number of cytokine genotypes in renal graft outcome of Australian transplant recipients.Using PCR-SSP, genotyping of cytokine polymorphisms were determined for 107 cadaveric kidney allograft recipients , performed between 1990 and 1998 in NSW. The following polymorphisms were investigated. TNFa (-238,-308), IL-10(-1082,-819,-592) IL-6 (-174), TGFβ 1 (Codon 10,25), IFNγ (+5644).A comparison of the gene frequencies of the cytokine alleles detected in the Australian population and other reported populations, was performed. The genotypes were then analysed with respect to graft outcome and the level of production of cytokine associated with each polymorphism as defined in the literature. The recipients were divided into two groups, rejectors and non-rejectors. Polymorphisms associated with TGFβ1, IFNγ , IL6 and TNFa were found to have no correlation with transplant outcome. However, the IL-10 high responder genotype showed a significant (p<0.0001) difference between and the two groups. More patients (51% rejectors and 13% non rejectors) with poor clinical outcome expressed the high responder genotype GCC/GCC (-1082, -819, -592).When the group of patients with the above genotype was further examined all patients that expressed the above genotype and were DR mismatched with their donor had a failed transplant. Those patients with the above genotype, and receiving a DR matched graft, had a significantly improved outcome.Analysis of our data confirms reports of other centres of the association of IL-10 gene polymorphisms and clinical outcome in HLA-DR mismatched transplants. For this reason, kidney recipients receiving HLA-DR mismatched transplants should be screened to determine their cytokine profile, to assist in the prediction of transplant outcome.