Fundamental role for HO-1 in the self-protection of renal allografts.
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) (<or=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 (<or=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.
Baan
Carla
C
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. c.c.baan@erasmusmc.nl
Peeters
Annemiek
A
Lemos
Francine
F
Uitterlinden
André
A
Doxiadis
Ilias
I
Claas
Frans
F
Ijzermans
Jan
J
Roodnat
Joke
J
Weimar
Willem
W
D006085:Graft Survival / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D016030:Kidney Transplantation; D008565:Membrane Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014184:Transplantation, Homologous; D019737:Transplants
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1