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

Tissue attenuates to injury by the effects of heme oxygenase (HO)-l. 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) (less than or equal to27) 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 (less than or equal to27 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% Cl 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% Cl 0.27-0.93, p = 0.03).