Clinical study: interventional cardiology
Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting

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Abstract

OBJECTIVES

To test the hypothesis that interleukin-1 receptor antagonist (IL-1ra) gene polymorphism contributes to the risk of restenosis after coronary 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 interleukin-1 receptor antagonist gene (IL-1RN) contains several well-characterized polymorphic sites that correlate with altered IL-1ra levels.

METHODS

In 1,850 consecutive patients, clinical and angiographic measures of restenosis were evaluated over one year after coronary stent placement. Repeat angiography at six months was achieved in 84% of the patients; angiographic restenosis was defined ≤50% diameter stenosis at follow-up. Genotyping for an exon 2 polymorphism (+2,018) of IL-1RN (alleles 1 and 2) was based on a polymerase chain reaction technique.

RESULTS

Allele 2 frequency was 0.28. Carriers of allele 2 had a significantly lower risk for angiographic restenosis, odds ratio (OR) of 0.78 (95% confidence 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 especially significant in patients <60 years (n = 696), with OR of 0.63 (0.43 to 0.91) for angiographic restenosis and 0.55 (0.39 to 0.78) for target vessel revascularization.

CONCLUSIONS

Allele 2 of the IL-1ra gene was associated with a lower incidence of restenosis after coronary stenting, particularly in younger patients. This finding supports a role of inflammation in the development of restenosis after stent placement.

Abbreviations

CI
confidence interval
IL-1
interleukin-1
IL-1ra
interleukin-1 receptor antagonist
IL-1RN
interleukin-1 receptor antagonist gene
MI
myocardial infarction
MLD
minimal lumen diameter
OR
odds ratio
PTCA
percutaneous transluminal coronary angioplasty
TVR
target vessel revascularization
VNTR
variable number tandem repeat

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