Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations

Authors

Ludmila Pawlikowska, University of California, San Francisco
Mary N. Tran, University of California, San Francisco
Achal S. Achrol, University of California, San FranciscoFollow
Charles E. McCulloch, University of California, San Francisco
Connie Ha, University of California, San Francisco
Denise L. Lind, University of California, San Francisco
Tomoki Hashimoto, University of California, San Francisco
Jonathan Zaroff, University of California, San Francisco
Michael T. Lawton, University of California, San FranciscoFollow
Douglas A. Marchuk, Duke University Medical Center
Pui Yan Kwok, University of California, San Francisco
William L. Young, University of California, San Francisco

Document Type

Article

Abstract

Background and Purpose - Accurate estimates of intracranial hemorrhage (ICH) risk in patients harboring brain arteriovenous malformation (BAVM) are needed to evaluate interventional strategies and to help guide clinical management. Identification of genetic polymorphisms associated with ICH would facilitate risk stratification in BAVM patients. Methods - We identified patients with BAVM and documented clinical presentation, demographic data, venous drainage pattern, and BAVM size. Patients were genotyped for 5 polymorphisms in 3 inflammatory cytokine genes, and 9 polymorphisms in 5 angiogenesis-related genes. Association of genotype with risk of hemorrhagic BAVM presentation was evaluated using logistic regression analysis. Results - We genotyped 180 patients with BAVM (53% female, 57% white, mean age at diagnosis 35±17 years, 41% presenting with ICH). BAVM patients homozygous for the interleukin 6 (IL6)-174G allele had a greater risk of ICH presentation (OR, 2.62, P=0.003) than IL6-174C carriers. In a multivariate logistic regression model, IL6-174G>C genotype, small BAVM size, and exclusively deep venous drainage were independent predictors of ICH presentation. A similar univariate trend was noted for the TNFα-308 GG genotype (P=0.055). The other polymorphisms genotyped were not associated with ICH. Conclusions - A polymorphism in the inflammatory cytokine IL6, but not polymorphisms in angiogenesis-related genes, was associated with ICH presentation of BAVM. Further studies are needed to define the role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage.

Publication Date

10-1-2004

Publication Title

Stroke

ISSN

00392499

Volume

35

Issue

10

First Page

2294

Last Page

2299

PubMed ID

15331795

Digital Object Identifier (DOI)

10.1161/01.STR.0000141932.44613.b1

Recommended Citation

Pawlikowska, Ludmila; Tran, Mary N.; Achrol, Achal S.; McCulloch, Charles E.; Ha, Connie; Lind, Denise L.; Hashimoto, Tomoki; Zaroff, Jonathan; Lawton, Michael T.; Marchuk, Douglas A.; Kwok, Pui Yan; and Young, William L., "Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations" (2004). Neurosurgery. 887.
https://scholar.barrowneuro.org/neurosurgery/887