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

被引:65
作者
Achrol, AS
Pawlikowska, L
McCulloch, CE
Poon, KYT
Ha, C
Zaroff, JG
Johnston, SC
Lee, C
Lawton, MT
Sidney, S
Marchuk, DA
Kwok, PY
Young, WL
机构
[1] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94110 USA
[2] Univ Calif San Francisco, Dept Perioperat Care, San Francisco, CA USA
[3] Univ Calif San Francisco, Cerebrovasc Res Ctr, San Francisco, CA USA
[4] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
[7] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[8] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA
[9] Kaiser Permanente, Med Care Program, Div Res, Oakland, CA USA
[10] Duke Univ, Med Ctr, Dept Genet, Durham, NC USA
关键词
cerebral hemorrhage; genetics; vascular malformations;
D O I
10.1161/01.STR.0000195133.98378.4b
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 chi(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-alpha-238G > A was associated with increased risk of new ICH after diagnosis (chi(2); 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. Conclusion - 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.
引用
收藏
页码:231 / 234
页数:4
相关论文
共 7 条
[1]  
Atkinson RP, 2001, STROKE, V32, P1430
[2]  
CHEN Y, 2005, ANN NEUROL 1108
[3]   Longitudinal risk of intracranial hemorrhage in patients with arteriovenous malformation of the brain within a defined population [J].
Halim, AX ;
Johnston, SC ;
Singh, V ;
McCulloch, CE ;
Bennett, JP ;
Achrol, AS ;
Sidney, S ;
Young, WL .
STROKE, 2004, 35 (07) :1697-1702
[4]   Mechanisms of disease - Inflammation, atherosclerosis, and coronary artery disease [J].
Hansson, GK .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (16) :1685-1695
[5]   Abnormal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in brain arteriovenous malformations [J].
Hashimoto, T ;
Wen, G ;
Lawton, MT ;
Boudreau, NJ ;
Bollen, AW ;
Yang, GY ;
Barbaro, NM ;
Higashida, RT ;
Dowd, CF ;
Halbach, VV ;
Young, WL .
STROKE, 2003, 34 (04) :925-930
[6]   Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations [J].
Pawlikowska, L ;
Tran, MN ;
Achrol, AS ;
McCulloch, CE ;
Ha, C ;
Lind, DL ;
Hashimoto, T ;
Zaroff, J ;
Lawton, MT ;
Marchuk, DA ;
Kwok, PY ;
Young, WL .
STROKE, 2004, 35 (10) :2294-2299
[7]   Promoter polymorphisms of the genes encoding tumor necrosis factor-α and interleukin-1β are associated with different subtypes of psoriasis characterized by early and late disease onset [J].
Reich, K ;
Mössner, R ;
König, IR ;
Westphal, G ;
Ziegler, A ;
Neumann, C .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (01) :155-163