Fundamental role for HO-1 in the self-protection of renal allografts

Am J Transplant. 2004 May;4(5):811-8. doi: 10.1111/j.1600-6143.2004.00420.x.

Abstract

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.

MeSH terms

  • Graft Survival / genetics
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Humans
  • Kidney / enzymology*
  • Kidney / metabolism
  • Kidney Transplantation*
  • Membrane Proteins
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Time Factors
  • Transplantation, Homologous
  • Transplants*

Substances

  • Membrane Proteins
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1