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


METHODS
In 1,850 consecutive patients, clinical and angiographic measures ofrestenosis 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 < or =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.
Kastrati
A
A
Deutsches Herzzentrum München and 1. Medizinische Klinik rechts der Isar, Technische Universität München, Munich, Germany. kastrati@dhm.mhn.de
Koch
W
W
Berger
P B
PB
Mehilli
J
J
Stephenson
K
K
Neumann
F J
FJ
von Beckerath
N
N
Böttiger
C
C
Duff
G W
GW
Schömig
A
A
D000368:Aged; D003327:Coronary Disease / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D012008:Recurrence; D012795:Sialoglycoproteins / Q000235:genetics / Q000494:pharmacology*; D015607:Stents
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins