Impact of donor and recipient cytokine genotypes on renal allograft outcome

Abstract

Allelic differences in gene promoter or codifying regions have been described to affect regulation of gene expression, consequently increasing or decreasing cytokine production and signal transduction responses to a given stimulus. This observation has been reported for interleukin (IL)-10 (−1082 A/G; −819/−592 CT/CA), transforming growth factor (TGF)-β (codon 10 C/T, codon 25 G/C), tumor necrosis factor (TNF)-α (−308 G/A), TNF-β (+252 A/G), interferon (IFN)-γ (+874 T/A), IL-6 (−174 G/C), and IL-4Rα (+1902 G/A). To evaluate the influence of these cytokine genotypes on the development of acute or chronic rejection, we correlated the genotypes of both kidney graft recipients and cadaver donors with the clinical outcome. Kidney recipients had 5 years follow-up, at least 2 HLA-DRB compatibilities, and a maximum of 25% anti-HLA pretransplantation sensitization. The clinical outcomes were grouped as follows: stable functioning graft (NR, n = 35); acute rejection episodes (AR, n = 31); and chronic rejection (CR, n = 31). The cytokine genotype polymorphisms were defined using PCR-SSP typing. A statistical analysis showed a significant prevalence of recipient IL-10 −819/−592 genotype among CR individuals; whereas among donors, the TGF-β codon 10 CT genotype was significantly associated with the AR cohort and the IL-6 −174 CC genotype with CR. Other albeit not significant observations included a strong predisposition of recipient TGF-β codon 10 CT genotype with CR, and TNF-β 252 AA with AR. A low frequency of TNF-α −308 AA genotype also was observed among recipients and donors who showed poor allograft outcomes.