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.


CONCLUSIONS
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.
Hoffmann
Steven
S
Transplantation Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Park
Jenny
J
Jacobson
Lynn M
LM
Muehrer
Rebecca J
RJ
Lorentzen
David
D
Kleiner
David
D
Becker
Yolanda T
YT
Hullett
Debra A
DA
Mannon
Roslyn
R
Kirk
Allan D
AD
Becker
Bryan N
BN
D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D005260:Female; D018740:Genetic Heterogeneity; D023281:Genomics; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000601:surgery; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014019:Tissue Donors; D014184:Transplantation, Homologous