Donor genomics influence graft events: the effect of donor polymorphisms on acute rejection and chronic allograft nephropathy

BACKGROUND: Organs procured from deceased donors emanate from individuals with diverse genetic backgrounds. Donor organs, therefore, may vary in their response to injury and immune stimuli in a genetically determined manner. We assessed polymorphisms from 244 renal allograft donors to better understand the impact of donor polymorphisms on selected transplant outcomes. METHODS: Donor genomic DNA restriction fragment length polymorphisms were assayed for evidence of common cytokine [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, TGF-beta, interferon (IFN)-gamma] and chemokine (CCR2, CCR5) polymorphisms. Associations between donor polymorphisms and graft events were determined using chi-square, linear regression, and Kaplan-Meier analyses. RESULTS: Several genotypic polymorphisms demonstrated a modest association with acute rejection, including the transforming growth factor (TGF)-beta T/C codon 10 (P= 0.027) and the CCR5 G/A 59029 (P= 0.039) genes by chi-square analysis. Notably, the presence of the T allele in the IFN-gamma gene (+874) demonstrated a highly significant association with biopsy-proven chronic allograft nephropathy (P < 0.008). This association remained highly significant in a multiple linear regression model that incorporated biopsy-proven acute rejection as a covariate. CONCLUSION: These data suggest that many of the donor polymorphisms studied in this analysis may influence a recipient's immune response to a renal allograft. However, their greatest impact may be demonstrated in long-term outcomes.