Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty.
OBJECTIVE
To determine if an association exists between postdilation restenosis and heme oxygenase-1 (HO-1), which is induced by balloon injury and inhibits neointimal formation through the action of endogenous carbon monoxide. A dinucleotide repeat in the promoter region of the HO-1 gene shows a length polymorphism that modulates the level of gene transcription.


METHODS
This cohort study included 96 consecutive patients (64 men; median age 69 years, interquartile range 60-75) who underwent successful balloon dilation in the femoropopliteal segment. Six-month patency was evaluated using oscillography, ankle-brachial index, and duplex sonography. The association of patency and the length of (GT) repeats in the HO-1 gene promoter was assessed in univariate and multivariate analyses.


RESULTS
Restenosis was found in 23 (24%) patients within the first 6 months. Patients with short (<25 GT) dinucleotide repeats in the HO-1 gene promoter on either allele had restenosis significantly less often than patients with longer (> or = 25 GT) dinucleotide repeats (p = 0.01). Multivariate analysis revealed a significantly reduced risk for restenosis in these patients compared to patients without the short allele (odds ratio 0.2, 95% Cl 0.06 to 0.70, p = 0.007).


CONCLUSIONS
Genetic risk factors for restenosis after percutaneous transluminal angioplasty have not been investigated. In this patient population, short repeat alleles of the heme oxygenase-1 gene promoter polymorphism were associated with reduced postdilation restenosis at 6 months. Upregulation of HO-1 may be an important protective factor after balloon angioplasty by inhibition of vascular smooth muscle cell proliferation.
Exner
M
M
Department of Laboratory Medicine, University of Vienna Medical School, Austria.
Schillinger
M
M
Minar
E
E
Mlekusch
W
W
Schlerka
G
G
Haumer
M
M
Mannhalter
C
C
Wagner
O
O
D000368:Aged; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000601:surgery*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011150:Popliteal Artery / Q000000981:diagnostic imaging / Q000601:surgery*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011859:Radiography; D013997:Time Factors; D014654:Vascular Patency / Q000235:genetics
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1