Candidate genetic markers and the risk of restenosis after coronary angioplasty

Abstract

The aim of the present study was to test for possible associations between candidate gene polymorphisms and the risk of restenosis and recurrent restenosis after percutaneous transluminal coronary angioplasty (PTCA) without stenting. We followed up 511 PTCA patients, and restenosis and recurrent restenosis were defined according to angiographical criteria. Genotyping of the beta-fibrinogen -455 G/A, glycoprotein (GP) IIIa PlA1/PlA2, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, factor V Leiden 1691 G/A, tumour necrosis factor alpha (TNFalpha) -238 G/A, TNFalpha -308 G/A, interleukin (IL)-1alpha -889 C/T, IL-1beta -511 C/T, methylenetetrahydrofolate reductase (MTHFR) 677 C/T and endothelial nitric oxide synthase (eNOS) 4 b/a gene polymorphisms was performed by PCR and restriction-fragment-length-polymorphism-based techniques. One hundred and sixty patients (31.3%) developed restenosis and in 130 of these patients, of whom 123 were available for analysis, a second PTCA without stenting was performed. Of these patients, 35 (28.5%) developed recurrent restenosis. None of the investigated genotypes were associated with the risk of restenosis or recurrent restenosis after PTCA. The degree of stenosis before and immediately after PTCA and the severity of the lesion were independent predictors for restenosis after PTCA. In conclusion, there was no association between the beta-fibrinogen -455 G/A, GP IIIa PlA1/A2, PAI-1 4G/5G, factor V Leiden 1691 G/A, TNFalpha -238 G/A, TNFalpha -308 G/A, IL-1alpha -889 C/T, the IL-1beta -511 C/T, MTHFR 677 C/T and eNOS 4 b/a gene polymorphisms and the risk of restenosis after PTCA as well as recurrent restenosis after repeated PTCA.

The interleukin 1B–511 polymorphism is associated with the risk of developing restenosis after coronary stenting in Mexican patients

“…Lack of association was reported for this polymorphism in patients with coronary heart disease [20,30], and lack of association between the IL-1B-511 polymorphism and restenosis was reported in patients after coronary angioplasty [26,27] and balloon angioplasty [31]. To our knowledge, this is the first time that an association between IL-1B-511 polymorphism and the risk of developing restenosis after coronary stenting is analyzed considering the type of stent that was implanted (BMS or DES).…”

The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

“…Factor V Leiden was associated in our study with protection against clinical restenosis. In a study by Volzke et al, 29 this association was not observed, but their study had limited statistical power and the genotype distribution of the Factor V Leiden polymorphism was not in Hardy-Weinberg equilibrium. The Factor V Leiden polymorphism is a well-known risk factor for venous thrombosis.…”

Genetic risk markers for post-angioplasty restenosis: what should we expect?

“…1.8. If correct, this puts the power of the study by Völzke et al [1] at the borderline for detection of such effects.…”

“…The authors [1] acknowledge that their study was powered to detect an odds ratio of 1.7-1.8 or greater for the effect of a given genetic polymorphism. Therefore we may ask ourselves whether we should expect a single polymorphism to have an effect of this size on such a complex disease, and whether knowing a patient's genotype will lead to a real benefit to the patient.…”

“…In this issue of Clinical Science, Völzke and co-workers [1] show that, in a group of over 500 patients with coronary artery disease (CAD), polymorphisms in a number of candidate genes were not associated with a risk of restenosis or recurrent restenosis after angioplasty, but the degree of stenosis immediately before or after the procedure and the severity of the lesion were independent predictors. The authors [1] acknowledge that their study was powered to detect an odds ratio of 1.7-1.8 or greater for the effect of a given genetic polymorphism.…”