Interleukin-1 receptor antagonist gene polymorphisms in carotid atherosclerosis.
OBJECTIVE
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.
Worrall
Bradford B
BB
University of Virginia, Departments of Neurology, Charlottesville, Va, USA.
Azhar
Salman
S
Nyquist
Paul A
PA
Ackerman
Robert H
RH
Hamm
Theresa L
TL
DeGraba
Thomas J
TJ
D000368:Aged; D000483:Alleles; D002340:Carotid Artery Diseases / Q000235:genetics*; D003710:Demography; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012372:ROC Curve; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins