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Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.

Publication ,  Journal Article
Achrol, AS; Pawlikowska, L; McCulloch, CE; Poon, KYT; Ha, C; Zaroff, JG; Johnston, SC; Lee, C; Lawton, MT; Sidney, S; Marchuk, DA; Kwok, P-Y ...
Published in: Stroke
January 2006

BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study.

Duke Scholars

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

January 2006

Volume

37

Issue

1

Start / End Page

231 / 234

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Time Factors
  • Risk
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Models, Statistical
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Achrol, A. S., Pawlikowska, L., McCulloch, C. E., Poon, K. Y. T., Ha, C., Zaroff, J. G., … UCSF BAVM Study Project, . (2006). Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. Stroke, 37(1), 231–234. https://doi.org/10.1161/01.STR.0000195133.98378.4b
Achrol, Achal S., Ludmila Pawlikowska, Charles E. McCulloch, KY Trudy Poon, Connie Ha, Jonathan G. Zaroff, S Claiborne Johnston, et al. “Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.Stroke 37, no. 1 (January 2006): 231–34. https://doi.org/10.1161/01.STR.0000195133.98378.4b.
Achrol, Achal S., et al. “Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.Stroke, vol. 37, no. 1, Jan. 2006, pp. 231–34. Pubmed, doi:10.1161/01.STR.0000195133.98378.4b.
Achrol AS, Pawlikowska L, McCulloch CE, Poon KYT, Ha C, Zaroff JG, Johnston SC, Lee C, Lawton MT, Sidney S, Marchuk DA, Kwok P-Y, Young WL, UCSF BAVM Study Project. Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. Stroke. 2006 Jan;37(1):231–234.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

January 2006

Volume

37

Issue

1

Start / End Page

231 / 234

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Time Factors
  • Risk
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Models, Statistical
  • Middle Aged
  • Male