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Fundamental Role for HO‐1 in the Self‐Protection of Renal Allografts
Author(s) -
Baan Carla,
Peeters Annemiek,
Lemos Francine,
Uitterlinden André,
Doxiadis Ilias,
Claas Frans,
Ijzermans Jan,
Roodnat Joke,
Weimar Willem
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00420.x
Subject(s) - medicine , urology
Tissue attenuates to injury by the effects of heme oxygenase (HO)‐1. The induction of HO‐1 expression is modulated by a (GT) n dinucleotide polymorphism in the promoter of the gene, of which increased activity is associated with short (S) (≤27) repeats. We investigated the influence of this HO‐1 gene polymorphism on renal transplant survival.DNA from 387 recipients and 384 donors was genotyped and we divided the HO‐1 alleles into two subclasses, the S (≤27 repeats) class and long (L) class (>27 repeats).Graft survival was associated with donor and not with recipient HO‐1 gene polymorphism (log rank p = 0.005; hazard ratio 0.51, 95% CI 0.32–0.83). The beneficial effect of the donor HO‐1 genotype was observed in grafts exposed to prolonged cold ischemia time and acute rejection. Patients who received a kidney from L ‐homozygotes lost their graft significantly more often to chronic allograft nephropathy (CAN) than carriers of S‐alleles (p = 0.015). Multivariate analysis showed reduced risk for graft failure in kidneys with S‐alleles in comparison to L ‐homozygotes (odds ratio 0.50, 95% CI 0.27–0.93, p = 0.03).Kidneys that are carriers of HO‐1 S‐allele are less vulnerable to tissue injury resulting in less CAN and better graft survival.