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(Stroke. 2003;34:790.)
© 2003 American Heart Association, Inc.

Research Reports

Interleukin-1 Receptor Antagonist Gene Polymorphisms in Carotid Atherosclerosis

Bradford B. Worrall, MD, MSc; Salman Azhar, MD; Paul A. Nyquist, MD; Robert H. Ackerman, MD; Theresa L. Hamm, RN Thomas J. DeGraba, MD

From the University of Virginia, Departments of Neurology and Health Evaluation Sciences (B.B.W.), Charlottesville, Va; Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Md (B.B.W., S.A., P.A.N., T.L.H., T.J.D.); Massachusetts General Hospital, Departments of Neurology and Neuroradiology, Boston (R.H.A.); and National Naval Medical Center, Bethesda, Md (T.L.H., T.J.D.).

Correspondence to Dr Thomas J. DeGraba, National Naval Medical Center, Clinical Stroke Research Unit, Neurology Department, Building 9, 2nd Deck, 8901 Wisconsin Ave, Bethesda, MD 20889-5600. E-mail TJDeGraba{at}bethesda.med.navy.mil

Abstract

Background and Purpose— Inflammation plays an important role in the development of atherosclerosis. The gene for the counterinflammatory cytokine interleukin–1 receptor antagonist (IL-1ra) is polymorphic, and high frequencies of allele 2 have been found to be associated with other inflammatory diseases. This study examined the association of allele and carrier frequencies of the IL-1ra gene with the presence of carotid atherosclerosis and plaque symptomaticity.

Methods— A total of 328 subjects identified as having carotid atherosclerosis or no atherosclerosis (controls) participated. Blood was obtained for DNA determination.

Results— Frequency of allele 2 was significantly greater in patients with atherosclerosis compared with nonatherosclerotic subjects. No difference was seen between symptomatic and asymptomatic atherosclerosis patients. Noncarriage of allele 2 was associated with reduced likelihood of atherosclerosis (odds ratio [OR], 0.44; 95% CI, 0.27 to 0.71). The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (unadjusted OR, 7.30; 95% CI, 2.31 to 22.94; adjusted OR, 13.78; 95% CI, 1.94 to 97.9). A gene-dose effect was detected.

Conclusions— These data suggest that allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis. Further investigation appears warranted.

Key Words: atherosclerosis • carotid artery diseases • cytokines • interleukin-1 receptor antagonist • polymorphism

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