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(Stroke. 2007;38:1189.)
© 2007 American Heart Association, Inc.

Original Contributions

IL1RN VNTR Polymorphism in Ischemic Stroke

Analysis in 3 Populations

Bradford B. Worrall, MD, MSc; Thomas G. Brott, MD; Robert D. Brown, Jr, MD; W. Mark Brown, MA; Stephen S. Rich, PhD; Sampath Arepalli, BS; Fabienne Wavrant-De Vrièze, PhD; Jaime Duckworth, MS; Andrew B. Singleton, PhD; John Hardy, PhD; James F. Meschia, MD for the SWISS, ISGS, and MSGD Investigators^*

From Departments of Neurology (B.B.W.) and Public Health Sciences (B.B.W.), University of Virginia Health System, Charlottesville, Va; Department of Neurology (T.G.B., J.F.M.), Mayo Clinic, Jacksonville, Fla; Department of Neurology (R.D.B.), Mayo Clinic, Rochester, Minn; Department of Public Health Sciences (W.M.B., S.S.R.), Wake Forest University, Winston-Salem, NC; National Institute on Aging (S.A., F.W.-D., J.D., A.B.S., J.H.), Neurogenetics Laboratory, Bethesda, Md.

Correspondence to James F. Meschia, MD, Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224. E-mail meschia.james{at}mayo.edu

Background and Purpose— Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease.

Methods— An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race.

Results— After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant.

Conclusions— Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted.

Key Words: atherosclerosis • genetics • IL-1 receptor antagonist • ischemia • stroke