Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty

Abstract

Background-Percutaneous transluminal coronary angioplasty (PTCA) is limited by the recurrence of luminal stenosis, which occurs in up to 50% of procedures. It has been shown that patient specific factors, perhaps genes, contribute to this process. Objective-To determine whether completion of healing after PTCA is part of an acute self limiting inflammatory process and whether polymorphism at important inflammatory gene loci might determine susceptibility to restenosis after PTCA. Design-DNA samples were collected from 171 patients attending for elective PTCA in Sheffield (S) and Leicester (L), who were scheduled to undergo follow up angiography (at four months (L) or six months (S)) as part of other restenosis studies. At follow up angiography, the patients were separated into restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loci (IL-1A (−889), IL-1B (−511), IL-1B (+3954), and IL-1RN intron 2 VNTR (variable number tandem repeat)) were genotyped using methods based on polymerase chain reaction. Significance was assessed by 2 analysis of the relevant contingency table, and the magnitude of eVect was estimated by calculating odds ratios. The Mantel-Haenszel (MH) test was applied to summarise data across the two populations. Results-Allele 2 at IL-1RN (IL-1RN*2) was significantly over represented in the non-restenoser group (L+S, 34% v 23% in restenosers). Furthermore, IL-1RN*2 homozygosity was increased in the non-restenoser population compared with the restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, single vessel disease only), and the eVect seemed to be restricted to the single vessel disease subpopulation. For other polymorphism within IL-1 related loci no significant associations were found with either restenosis or non-restenosis. Conclusions-IL-1RN*2 may be associated with protection from restenosis after PTCA for individuals with single vessel disease. As this polymorphism has functional significance, this finding suggests that alteration in an individual's inflammatory predisposition may modulate the blood vessel response to injury. (Heart 2001;86:336-340)

A Functional Interleukin-1 Receptor Antagonist Polymorphism Influences Atherosclerosis Development The Interleukin-1.BETA.:Interleukin-1 Receptor Antagonist Balance in Atherosclerosis

“…This finding substantiates previous reports of slower progression of restenosis after coronary angioplasty in individuals carrying the 2-repeat allele. [43][44][45] Others have shown that systemic levels of IL-1Ra are increased in carriers of the 2-repeat allele. 46 Hence, the polymorphism of IL-1Ra can alter the baseline balance between IL-1Ra and IL-1β and increase the IL-1Ra :IL-1β ratio.…”

O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana

“…Indications for coronary arteriography in our clinic are based on guidelines for coronary angiography 14 . According to coronary angiography results 12,15 participants who presented ≥ 70 % stenoses in at least one of the major coronary arteries were considered as CAD (n= 257) and the remainders who presented ≤ 30 % stenosis were accepted in the normal group (n= 170). CAD group was divided into two subgroups: SVD (only one coronary artery stenosis; n= 91) and Multiple Vessel Disease (MVD; more than one coronary artery stenosis; n= 166).…”

“…Furthermore, it has been reported that IL1RN 2 allele is significantly associated with CAD in the Type 2 diabetes patients 11 . Also, IL1RN 2 allele has a protective effect on restenosis after PTCA 12 and an association between IL1RN 2 and carotid atherosclerosis was reported 22 . It was also reported that future Myocardial Infarction risk was increased with IL1RN 2 allele and high CRP levels in young patients 23 .…”

Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries

“…IL-1 is a strong contributor to the development of restenosis (5,15) through induction and nuclear translocation of NF-B (23) and increased expression of platelet-derived growth factor and fibroblast growth factor (FGF) (9), and, most notably, IL-1␣ can recruit and activate macrophages, which are the richest cellular source of growth factors in the body (4). Indeed, there is a direct correlation between inflammatory cell infiltration and neointimal formation at the site of vascular intervention (18).…”