Heme Oxygenase-1 Gene Promoter Microsatellite Polymorphism is Associated with Restenosis after Percutaneous Transluminal Angioplasty

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Abstract
Purpose: 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 (≥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% CI 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.