Published Online
on February 20, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on September 24, 2002
Accepted on September 26, 2002

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; and 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.).

^* To whom correspondence should be addressed. E-mail: TJDeGraba{at}bethesda.med.navy.mil.

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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