Clinical Restenosis after Coronary Stent Implantation Is Associated with the Heme Oxygenase-1 Gene Promoter Polymorphism and the Heme Oxygenase-1 +99G/C Variant

Abstract

Background: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. Methods: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 ؉99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. Results: Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR) ‫؍‬ 1.9; 95% confidence interval (95% CI), 1.0 -3.4; P ‫؍‬ 0.04]. Interestingly, the allele longer than 29

Hemin prevents in-stent stenosis in rat and rabbit models by inducing heme-oxygenase-1

“…SnPPIX alone worsened stenosis, suggesting that endogenous HO might also limit ISS. In this regard, recent studies demonstrated a greater occurrence of in-stent coronary stenosis associated with a ho-1 gene promoter polymorphism, 27,28 although another report cast doubt on this association. 29 We further assessed the activity of HO-1 by measuring the byproducts of heme degradation, such as CO and bilirubin.…”

Heme Oxygenase 1 Polymorphisms and Plasma Concentrations in Critically Ill Patients

“…The +99G/C polymorphism causes a change of aspartic acid to histidine at amino acid position 7 of the HO-1 protein. Gulesserian et al have also found linkage disequilibrium between the GT n and the +99G/C polymorphism (29), but neither the frequency nor the functionality of the +99G/C polymorphism has been investigated in other clinical studies. Because of the perfect LD of the +99C with the long GT allele, it remains to be elucidated which one of these two polymorphisms is functionally more important.…”

Hemoxygenase-1 in Cardiovascular Disease

“…Others (74,75) have also looked at this polymorphism in CAD and/or diabetes mellitus, speculating that diabetic persons carrying longer (GT) repeats might have higher oxidative stress and increased susceptibility to the development of CAD (i.e., the patients with fewer GT repeats were less likely to have CAD). The long (Ͼ29 repeats) polymorphic allele of the HO-1 gene promoter, which leads to low HO-1 inducibility, may be an independent prognostic marker for restenosis after percutaneous coronary intervention and stent implantation (76). Another polymorphism [the T(Ϫ413)A (AA/ TAϩTT) variant] of the HO-1 gene is associated with an increased incidence of hypertension in women (77).…”