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Cerebrovasc Dis. 2009;27(2):176-82. doi: 10.1159/000185609. Epub 2008 Dec 18.

Common variants in interleukin-1-Beta gene are associated with intracranial hemorrhage and susceptibility to brain arteriovenous malformation.

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  • 1Center 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

Abstract

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.

METHOD:

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).

CONCLUSION:

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.

Copyright (c) 2008 S. Karger AG, Basel.

PMID:
19092239
[PubMed - indexed for MEDLINE]
PMCID:
PMC2649796
Free PMC Article

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