IL1RN VNTR polymorphism in ischemic stroke: analysis in 3 populations.
OBJECTIVE
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.
Worrall
Bradford B
BB
Department of Neurology, University of Virginia Health System, Charlottesville, VA, USA.
Brott
Thomas G
TG
Brown
Robert D
RD
Brown
W Mark
WM
Rich
Stephen S
SS
Arepalli
Sampath
S
Wavrant-De Vrièze
Fabienne
F
Duckworth
Jaime
J
Singleton
Andrew B
AB
Hardy
John
J
Meschia
James F
JF
D000368:Aged; D002545:Brain Ischemia / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009656:North America; D011110:Polymorphism, Genetic / Q000235:genetics*; D035781:Siblings; D020521:Stroke / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D044465:White People
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein