TY - JOUR
T1 - Fundamental Role for HO-1 in the Self-Protection of Renal Allografts
AU - Baan, Carla
AU - Peetersa, Annemiek
AU - Lemos, Francine
AU - Uitterlinden, André
AU - Doxiadis, Ilias
AU - Claas, Frans
AU - Ijzermans, Jan
AU - Roodnat, Joke
AU - Weimar, Willem
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=2442613127&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2004.00420.x
DO - 10.1111/j.1600-6143.2004.00420.x
M3 - Article
C2 - 15084179
SN - 1600-6135
VL - 4
SP - 811
EP - 818
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -