肿瘤坏死因子-α -238G>A多态性及载脂蛋白E2多态性与脑动静脉畸形治疗后颅内出血的相关性
Association of tumor necrosis factor-alpha-238G>A and apolipoprotein E2 polymorphisms with intracranial hemorrhage after brain arteriovenous malformation treatment.
作者信息
Achrol Achal S, Kim Helen, Pawlikowska Ludmila, Trudy Poon K Y, McCulloch Charles E, Ko Nerissa U, Johnston S Claiborne, McDermott Michael W, Zaroff Jonathan G, Lawton Michael T, Kwok Pui-Yan, Young William L
机构信息
Center for Cerebrovascular Research and Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94110, USA.
出版信息
Neurosurgery. 2007 Oct;61(4):731-9; discussion 740. doi: 10.1227/01.NEU.0000298901.61849.A4.
OBJECTIVE
We previously reported specific genotypes of polymorphisms in two genes, tumor necrosis factor-alpha (TNF-alpha-238G > A) and Apolipoprotein E (ApoE e2), as independent predictors of new intracranial hemorrhage (ICH) in the natural course of untreated brain arteriovenous malformations. We hypothesized that the risk of posttreatment ICH would also be greater in patients with brain arteriovenous malformations with these genotypes.
METHODS
Two hundred fifteen patients undergoing brain arteriovenous malformation treatment (embolization, arteriovenous malformation resection, radiosurgery, or any combination of these) were genotyped and followed longitudinally. Association of genotype with new symptomatic ICH after initiation of treatment was assessed using Cox proportional hazards adjusted for treatment type, demographics, and established ICH risk factors censored at the time of the last follow-up evaluation or death.
RESULTS
The cohort was 48% male and 55% Caucasian, and 52% had an ICH before the initiation of treatment; the mean age +/- standard deviation was 36.6 +/- 17.2 years. Posttreatment ICH occurred in 34 (16%) patients with a median follow-up period of 1.9 years (interquartile range, 1.6 yr). After adjustment, the risk of posttreatment ICH was greater for TNF-alpha-238 AG genotype (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.3-9.8; P = 0.016) and ApoE e2 (HR, 3.2; 95% CI, 1.0-9.7; P = 0.042). Similar trends for the TNF-alpha-238 AG genotype were seen in surgery (HR, 4.2; 95% CI, 0.6-28.8; P = 0.14) and radiosurgery subsets (HR, 3.8; 95% CI, 0.7-19.4; P = 0.11). An effect of ApoE e2 was seen in radiosurgery subsets (HR, 10.9; 95% CI, 1.3-93.7; P = 0.030), but not in surgery subsets (HR, 1.4; 95% CI, 0.3-7.4; P = 0.67).
CONCLUSION
Despite a variety of different mechanisms for posttreatment hemorrhage, these data suggest that the TNF-alpha and ApoE genotypes may contribute common phenotypes of enhanced vascular instability that increase the risk of hemorrhagic outcome.
目的
我们之前报道过两个基因（肿瘤坏死因子-α（TNF-α -238G>A）和载脂蛋白E（ApoE e2））多态性的特定基因型，是未经治疗的脑动静脉畸形自然病程中发生新的颅内出血（ICH）的独立预测因素。我们推测，具有这些基因型的脑动静脉畸形患者治疗后发生ICH的风险也会更高。
方法
对215例接受脑动静脉畸形治疗（栓塞、脑动静脉畸形切除术、放射外科手术或这些方法的任意组合）的患者进行基因分型并进行纵向随访。使用Cox比例风险模型评估基因型与治疗开始后新出现的有症状ICH之间的关联，该模型针对治疗类型、人口统计学特征以及在最后一次随访评估或死亡时审查的已确定的ICH风险因素进行了调整。
结果
该队列中48%为男性，55%为白种人，52%在治疗开始前发生过ICH；平均年龄±标准差为36.6±17.2岁。34例（16%）患者发生了治疗后ICH，中位随访期为1.9年（四分位间距为1.6年）。调整后，TNF-α -238 AG基因型（风险比[HR]，3.5；95%置信区间[CI]，1.3 - 9.8；P = 0.016）和ApoE e2（HR，3.2；95% CI，1.0 - 9.7；P = 0.042）的患者发生治疗后ICH的风险更高。在手术亚组（HR，4.2；95% CI，0.6 - 28.8；P = 0.14）和放射外科手术亚组（HR，3.8；95% CI，0.7 - 19.4；P = 0.11）中观察到TNF-α -238 AG基因型有类似趋势。在放射外科手术亚组中观察到ApoE e2的影响（HR，10.9；95% CI，1.3 - 93.7；P = 0.030），但在手术亚组中未观察到（HR，1.4；95% CI，0.3 - 7.4；P = 0.67）。
结论
尽管治疗后出血有多种不同机制，但这些数据表明，TNF-α和ApoE基因型可能导致血管不稳定性增强的共同表型，从而增加出血性结局的风险。
Zotero 插件