Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor.
OBJECTIVE
We investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty.


BACKGROUND
Heme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats.


METHODS
We studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis.


RESULTS
Restenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis.


CONCLUSIONS
The HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty.
Schillinger
Martin
M
Angiology, Department of Laboratory Medicine, University of Vienna, Medical Faculty, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Exner
Markus
M
Minar
Erich
E
Mlekusch
Wolfgang
W
Müllner
Marcus
M
Mannhalter
Christine
C
Bach
Fritz H
FH
Wagner
Oswald
O
D000368:Aged; D000800:Angioplasty, Balloon; D001317:Austria / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000628:therapy*; D023903:Coronary Restenosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008565:Membrane Proteins; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1