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

Steven Hoffmann, Jenny Park, Lynn M. Jacobson, Rebecca J. Muehrer, David Lorentzen, David Kleiner, Yolanda T. Becker, Debra A. Hullett, Roslyn Mannon, Allan D. Kirk, Bryan N. Becker

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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)-α, TGF-β, interferon (IFN)-γ] 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)-β 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-γ 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.

Original languageEnglish (US)
Pages (from-to)1686-1693
Number of pages8
JournalKidney International
Volume66
Issue number4
DOIs
StatePublished - Oct 2004

Keywords

  • Donor populations
  • Gene polymorphisms
  • Kidney transplantation

ASJC Scopus subject areas

  • Nephrology

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