Common variants in interleukin-1-Beta gene are associated with intracranial hemorrhage and susceptibility to brain arteriovenous malformation.
BACKGROUND
Polymorphisms in the proinflammatory cytokine interleukin (IL)-1beta gene have been associated with systemic atherogenesis, thrombosis and rupture. The aim of this study was to investigate associations between single nucleotide polymorphisms (SNPs) in IL-1beta and intracranial hemorrhage (ICH) in the natural course of brain arteriovenous malformation (BAVM) patients.


METHODS
Two IL-1beta promoter SNPs (-511C-->T, -31T-->C) and 1 synonymous coding SNP in exon 5 at +3953C-->T (Phe) were genotyped in 410 BAVM patients. We performed a survival analysis of time to subsequent ICH, censoring cases at first treatment, death or last follow-up. A Cox regression analysis was performed to obtain hazard ratios (HRs) for genotypes adjusted for age, sex, Caucasian race/ethnicity and hemorrhagic presentation.


RESULTS
Subjects with the -31 CC genotype (HR = 2.7; 95% CI 1.1-6.6; p = 0.029) or the -511 TT genotype (HR = 2.6; 95% CI 1.1-6.5; p = 0.039) had a greater risk of subsequent ICH compared with reference genotypes, adjusting for covariates. The +3953C-->T SNP was not significantly associated with an increased ICH risk (p = 0.22). The IL-1beta promoter polymorphisms were also associated with BAVM susceptibility among a subset of 235 BAVM cases and 255 healthy controls of Caucasian race/ethnicity (p < 0.001).


CONCLUSIONS
IL-1beta promoter polymorphisms were associated with an increased risk of ICH in BAVM clinical course and with BAVM susceptibility. These results suggest that inflammatory pathways, including the IL-1beta cytokine, may play an important role in ICH.
Kim
Helen
H
Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA. ccr@anesthesia.ucsf.edu
Hysi
Pirro G
PG
Pawlikowska
Ludmila
L
Poon
Annie
A
Burchard
Esteban González
EG
Zaroff
Jonathan G
JG
Sidney
Stephen
S
Ko
Nerissa U
NU
Achrol
Achal S
AS
Lawton
Michael T
MT
McCulloch
Charles E
CE
Kwok
Pui-Yan
PY
Young
William L
WL
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012044:Regression Analysis; D055815:Young Adult
D053583:Interleukin-1beta