Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty

Background-Percutaneous transluminal coronary angioplasty (PTCA) is limited by the recurrence of luminal stenosis, which occurs in up to 50% of proced ures. It has been shown that patient specific factors, perhaps genes, contr ibute 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 imp ortant 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 foll ow up angiography (at four months (L) or six months (S)) as part of other r estenosis studies. At follow up angiography, the patients were separated in to restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loc i (IL-1A (-889), IL-1B (-511), IL-1B (+3954), and IL-1RN intron 2 VNTR (var iable number tandem repeat)) were genotyped using methods based on polymera se chain reaction. Significance was assessed by <chi>(2) analysis of the re levant contingency table, and the magnitude of effect was estimated by calc ulating odds ratios. The Mantel-Haenszel (NIH) test was applied to summaris e 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% upsilon 23% in restenosers). Furthermor e. IL-1RN*2 homozygosity was increased in the non-restenoser population com pared with the restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, sing le vessel disease only), and the effect seemed to be restricted to the sing le 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 afte r PTCA for individuals with single vessel disease. As this polymorphism has functional significance, this finding suggests that alteration in an indiv idual's inflammatory predisposition may modulate the blood vessel response to injury.