Donor heme oxygenase-1 genotype is associated with renal allograft function.
BACKGROUND
The heme oxygenase (HO) isoenzyme HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study we investigated the impact of the promoter polymorphism of kidney allograft donors on clinical outcomes after transplantation.


METHODS
We enrolled 101 recipients of cadaveric donor kidney allografts (who underwent transplantation between June 1998 and September 1999) in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes.


RESULTS
Fifty patients (49.5%) had received a kidney from a donor with at least one class S allele. Recipients of allografts from a class S allele carrier had significantly lower 1-year serum creatinine levels (median 1.46 mg/dL, interquartile range 1.17-1.68 mg/dL) compared with recipients of a non-class S allele donor kidney (median 1.61 mg/dL, interquartile range 1.38-2.22 mg/dL, P =0.01). After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70-0.95, P =0.01) those of recipients of a non-class S allele transplant. The two patient groups did not differ significantly with respect to the incidence of delayed graft function, allograft rejection, or immunologic graft loss.


CONCLUSIONS
Our data suggest an influence of the HO-1 gene promoter polymorphism on kidney allograft function and thus support previous studies indicating a protective effect of HO-1 induction in organ transplantation.
Exner
Markus
M
Department of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria.
Böhmig
Georg A
GA
Schillinger
Martin
M
Regele
Heinz
H
Watschinger
Bruno
B
Hörl
Walter H
WH
Raith
Marianne
M
Mannhalter
Christine
C
Wagner
Oswald F
OF
D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1