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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hoffmann, S; Park, J; Jacobson, LM; Muehrer, RJ; Lorentzen, D; Kleiner, D; Becker, YT; Hullett, DA; Mannon, R; Kirk, AD; Becker, BN

Published Date

  • October 2004

Published In

Volume / Issue

  • 66 / 4

Start / End Page

  • 1686 - 1693

PubMed ID

  • 15458467

Pubmed Central ID

  • 15458467

International Standard Serial Number (ISSN)

  • 0085-2538

Digital Object Identifier (DOI)

  • 10.1111/j.1523-1755.2004.00936.x

Language

  • eng

Conference Location

  • United States