Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty

Purpose: To determine if an association exists between postdilation resteno sis and heme oxygenase-1 (HO-1), which is Induced by balloon injury and inh ibits neointimal formation through the action of endogenous carbon monoxide . A dinucleotide repeat in the promoter region of the HO-1 gene shows a len gth 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 us ing oscillography, ankle-brachial index, and duplex sonography. The associa tion of patency and the length of (GT) repeats in the HO-1 gene promoter wa s assessed in univariate and multivariate analyses. Results: Restenosis was found in 23 (24%) patients within the first 6 month s. Patients with short (< 25 GT) dinucleotide repeats in the HO-1 gene prom oter on either allele had restenosis. significantly less often than patient s with longer ( greater than or equal to 25 GT) dinucleotide repeats (p = 0 .01). Multivariate analysis revealed a significantly reduced risk for reste nosis 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 translu minal angioplasty have not been investigated. In this patient population, s hort 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.