Association of functional heme oxygenase-1 gene promoter polymorphism with renal transplantation outcomes

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)(n) polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele < 25) increases transcription. The role of this HO-1 gene promoter polymorphism on renal transplant outcomes was assessed. DNA from 707 donor/recipient pairs (n = 1414) of first deceased donor renal transplants (99% Caucasian) was genotyped. Graft survival was not significantly impacted by carriage of an S-allele by the donor (hazard ratio 0.89, 95% CI 0.71-1.11; p = 0.28) or recipient (hazard ratio 1.19, 95% CI 0.95-1.48; p = 0.13). Similarly neither donor nor recipient genotype influenced recipient survival (hazard ratio 0.89, 95% CI 0.67-1.18; p = 0.41, and hazard ratio 1.22, 95% CI 0.93-1.62; p = 0.16). The hazard ratios changed only minimally in multivariate analysis including significant survival factors. Genotype did not alter the incidence of acute rejection or chronic allograft nephropathy. There is no evidence of a protective effect for the S-allele of the HO-1 gene promoter polymorphism on graft or recipient survival in clinical renal transplantation.