Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting

OBJECTIVES To test the hypothesis that interleukin-1 receptor antagonist (I L-1ra) gene polymorphism contributes to the risk of restenosis after corona ry stenting. BACKGROUND Cytokines of the interleukin-1 (IL-1) family play a central role in regulating inflammatory responses. There is strong evidence to support IL-1 involvement in smooth muscle cell mitogenesis and extracellular matrix metabolism. The IL-1ra counters the proinflammatory effects of IL-1. The i nterleukin-1 receptor antagonist gene (IL-1RN) contains several well-charac terized polymorphic sites that correlate with altered IL-1ra levels. METHODS In 1,850 consecutive patients, clinical and angiographic measures o f restenosis were evaluated over one year after coronary stent placement. R epeat angiography at six months was achieved in 84% of the patients; angiog raphic restenosis was defined less than or equal to 50% diameter stenosis a t follow-up. Genotyping for an exon 2 polymorphism (+2,018) of IL-1RN (alle les 1 and 2) was based on a polymerase chain reaction technique. RESULTS Allele 2 frequency was 0.28. Carriers of allele 2 had a significant ly lower risk for angiographic restenosis, odds ratio (OR) of 0.78 (95% con fidence interval, 0.63 to 0.97) and target vessel revascularization, OR of 0.73 (0.58 to 0.92) compared with noncarriers. Risk reduction was especiall y significant in patients <60 years (n = 696), with OR of 0.63 (0.43 to 0.9 1) for angiographic restenosis and 0.55 (0.39 to 0178) for target vessel re vascularization. CONCLUSIONS Allele 2 of the IL-1ra gene was associated with a lower inciden ce of restenosis after coronary stenting, particularly in younger patients. This finding supports a role of inflammation in the development of resteno sis after stent placement. (C) 2000 by the American College of Cardiology.