Genetic susceptibility factors for restenosis after coronary angioplasty

Background. Percutaneous transluminal coronary angioplasty (PTCA) has become an established treatment for patients with atherosclerotic coronary artery lesions. However, the extent of this procedure is weakened by restenosis that occurs within 6 months after PTCA. Recently, intracoronary stent implantation has been shown to significantly reduce angiographic restenosis. Not all subjects develop restenosis, suggesting that predisposing factors may underlie this phenomenon. Based on a candidate gene research strategy, we sought associations between restenosis after PTCA and various genetic polymorphisms. Patients and Methods. More than 200 patients with PTCA and 200 patients with PTCA and coronary stenting were enrolled. Quantitative angiographic variables from computer-assisted coronary angiography were measured before and 6 months after angioplasty, in patients with and without stent implantation. DNA samples were recovered from each patient and genetic polymorphisms were characterised. Results. We demonstrated that the deletion (D) allele of the angiotensin-I converting enzyme (ACE) gene, associated with increased levels of circulating and cellular enzyme, was not a risk factor for restenosis after PTCA. We reported that this polymorphism was associated with an increased risk of coronary artery occlusion after PTCA. Conversely, the ACE D allele was a major risk factor for restenosis after stent implantation, suggesting a possible association with neointimal hyperplasia, a predominant mechanism of restenosis after stenting. Conclusions. The ACE D allele is a major risk factor for restenosis after coronary stenting and thus may be proposed to trace subjects at risk. ACE inhibitors may also be tested to reduce restenosis after coronary stenting particularly in D allele bearer subjects.