CLINICAL STUDY: INTERVENTIONAL CARDIOLOGY
Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting
Adnan Kastrati, MD*,
Werner Koch, PhD*,
Peter B. Berger, MD ,
Julinda Mehilli, MD*,
Katherine Stephenson, PhD ,
Franz-Josef Neumann, MD*,
Nicolas von Beckerath, MD*,
Corinna Böttiger, MD*,
Gordon W. Duff, MD, PhD and
Albert Schömig, MD*
* Deutsches Herzzentrum München and 1. Medizinische Klinik rechts der Isar, Technische Universität Müchen, Munich, Germany
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
Interleukin Genetics, Inc., San Antonio, Texas, USA
Division of Molecular and Genetic Medicine, University of Sheffield, Sheffield, United Kingdom
Manuscript received April 5, 2000;
revised manuscript received June 28, 2000,
accepted August 31, 2000.
Reprint requests and correspondence: Dr. Adnan Kastrati, Deutsches Herzzentrum, München, Lazarettstrasse 36, 80636 München, Germany
kastrati{at}dhm.mhn.de
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.
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Abbreviations and Acronyms
| | 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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