Tumor Necrosis Factor-α–238G>A Promoter Polymorphism Is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations
| Autor: | Michael T. Lawton, Achal S. Achrol, K. Y.Trudy Poon, Douglas A. Marchuk, William L. Young, S. Claiborne Johnston, Pui-Yan Kwok, Chanhung Lee, Connie Ha, Stephen Sidney, Ludmila Pawlikowska, Charles E. McCulloch, Jonathan G. Zaroff |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Risk medicine.medical_specialty Pathology Time Factors Genotype Hemorrhage Single-nucleotide polymorphism Polymorphism Single Nucleotide Gastroenterology Arteriovenous Malformations Central nervous system disease Internal medicine medicine Humans Promoter Regions Genetic Stroke Proportional Hazards Models Advanced and Specialized Nursing Models Statistical Interleukin-6 Tumor Necrosis Factor-alpha Proportional hazards model Vascular disease business.industry Haplotype Brain Arteriovenous malformation Middle Aged medicine.disease Haplotypes Female Neurology (clinical) Cardiology and Cardiovascular Medicine business |
| Zdroj: | Stroke. 37:231-234 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/01.str.0000195133.98378.4b |
| Popis: | 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-α (TNF-α–238G>A; TNF-α–308G>A). Association of genotype with risk of new ICH was screened using χ 2 ; 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-α–238G>A was associated with increased risk of new ICH after diagnosis (χ 2 ; P =0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-α–238 AG genotype (hazard ratio, 4.01; P =0.015). No other SNP was found to be associated with new ICH. Conclusion— A TNF-α 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. |
| Databáze: | OpenAIRE |
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