Microsatellite polymorphism in the heme oxygenase-1 gene promoter and cardiac allograft vasculopathy.
BACKGROUND
The heme oxygenase-1 (HO-1) isoenzyme 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 on the development of cardiac allograft vasculopathy (CAV) in human heart transplants.


METHODS
We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV.


RESULTS
Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30).


CONCLUSIONS
In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.
Ullrich
Robert
R
Clinical Department of Pathology, Medical University Vienna, Vienna, Austria.
Exner
Markus
M
Schillinger
Martin
M
Zuckermann
Andreas
A
Raith
Marianne
M
Dunkler
Daniela
D
Horvat
Reinhard
R
Grimm
Michael
M
Wagner
Oswald
O
D000328:Adult; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D016027:Heart Transplantation / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D015854:Up-Regulation / Q000235:genetics
D051547:Heme Oxygenase-1