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

Donor genomics influence graft events: The effect of donor polymorphisms on acute rejection and chronic allograft nephropathy. Organs procured from deceased donors emanate from individuals with diverse genetic backgrounds. Donor organs, therefore, may vary in their response to injury and immune stim...

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Bibliographic Details
Published in:Kidney international 2004-10, Vol.66 (4), p.1686-1693
Main Authors: Hoffmann, Steven, Park, Jenny, Jacobson, Lynn M., Muehrer, Rebecca J., Lorentzen, David, Kleiner, David, Becker, Yolanda T., Hullett, Debra A., Mannon, Roslyn, Kirk, Allan D., Becker, Bryan N.
Format: Article
Language:English
Subjects:
Acute Disease
Adult
Biological and medical sciences
Chronic Disease
donor populations
Female
gene polymorphisms
Genetic Heterogeneity
Genomics
Graft Rejection - genetics
Graft Survival - genetics
Humans
Kidney Diseases - genetics
Kidney Diseases - surgery
Kidney Transplantation
Linear Models
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Polymorphism, Genetic
Renal failure
Tissue Donors
Transplantation, Homologous
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Summary:Donor genomics influence graft events: The effect of donor polymorphisms on acute rejection and chronic allograft nephropathy. 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. 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. 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. 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.
ISSN:0085-2538
1523-1755
DOI:10.1111/j.1523-1755.2004.00936.x