(Circulation. 1999;99:861-866.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Interleukin-1 Receptor Antagonist Gene Polymorphism and Coronary Artery Disease
From the Divisions of Clinical Sciences (N.G.H.T.) (S.E.F., R.M.D., J.G., D.C. Cumberland, D.C. Crossman) and Molecular and Genetic Medicine (N.J.C., G.W.D.), University of Sheffield, UK; the Department of Medical Genetics (P.S., N.D.C., S.J.) and Department of Cardiological Sciences (J.C.K.), St George's Hospital Medical School, London, UK.
Correspondence to Prof D.C. Crossman, Cardiovascular Medicine, Division of Clinical Sciences (N.G.H.T.), Clinical Sciences Centre, University of Sheffield, Northern General Hospital, Sheffield, S5 7AU, UK. E-mail D.C.Crossman{at}Sheffield.ac.uk
Background—Cytokine gene
variations are contributory factors in inflammatory pathology.
Allele frequencies of interleukin (IL)-1 cluster genes
[IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and
tissue necrosis factor (TNF)-
gene [TNFA(-308)] were measured in
healthy blood donors (healthy control subjects), patients with
angiographically normal coronary arteries (patient control
subjects), single-vessel coronary disease (SVD), and those with
multivessel coronary disease (MVD).
Methods and Results—Five hundred fifty-six patients attending for
coronary angiography in Sheffield were studied: 130 patient
control subjects, 98 SVD, and 328 MVD. Significant associations were
tested in an independent population (London) of 350: 57 SVD, 191 MVD,
and 102 control subjects. IL-1RN*2 frequency in Sheffield patient
control subjects was the same as in 827 healthy control subjects.
IL-1RN*2 was significantly overrepresented in Sheffield SVD
patients (34% vs 23% in patient control subjects); IL-1RN*2
homozygotes in the SVD population (
2 carriage=8.490, 1
df, P=0.0036). This effect was
present though not quite significant in the London population
(P=0.0603). A summary trend test of the IL-1RN SVD
genotype data for Sheffield and London showed a significant
association with *2 (P=0.0024). No significant effect of
genotype at IL-1RN was observed in the Sheffield or London MVD
populations. Genotype distribution analysis comparing
the SVD and MVD populations at IL-1RN showed a highly significant trend
(P=0.0007) with the use of pooled data. No significant
associations were seen for the other polymorphisms.
Conclusions—IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.
Key Words: interleukins • genes • coronary artery disease
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