TY - JOUR
T1 - Donor genomics influence graft events
T2 - The effect of donor polymorphisms on acute rejection and chronic allograft nephropathy
AU - Hoffmann, Steven
AU - Park, Jenny
AU - Jacobson, Lynn M.
AU - Muehrer, Rebecca J.
AU - Lorentzen, David
AU - Kleiner, David
AU - Becker, Yolanda T.
AU - Hullett, Debra A.
AU - Mannon, Roslyn
AU - Kirk, Allan D.
AU - Becker, Bryan N.
N1 - Funding Information:
This work was supported in part by NIH grants 1RO1 AI-45925–04 and 5K24 DK616962-02 (BNB). We thank the coordinators, nurses, and staff of the University of Wisconsin Transplant Program and the NIDDK Organ-Tissue Transplant Research Center for their efforts in coordinating and providing clinical and research samples. We are appreciative of the expert technical assistance provided by Seleem Sayaar and Olivia Chang, and the statistical assistance provided by Roger Brown.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
KW - Donor populations
KW - Gene polymorphisms
KW - Kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=4644344876&partnerID=8YFLogxK
U2 - 10.1111/j.1523-1755.2004.00936.x
DO - 10.1111/j.1523-1755.2004.00936.x
M3 - Article
C2 - 15458467
AN - SCOPUS:4644344876
SN - 0085-2538
VL - 66
SP - 1686
EP - 1693
JO - Kidney International
JF - Kidney International
IS - 4
ER -