Apolipoprotein E and Outcomes in Subarachnoid Hemorrhage

描述(申请人提供)：蛛网膜下腔出血(SAH)占65岁之前中风患者潜在寿命损失的近三分之一，每年造成的经济负担估计超过50亿美元。在预测因功能和认知障碍而导致的长期残疾方面，预后指标一直不可靠。使用像载脂蛋白E(APOE)基因这样的遗传预测因子将有助于我们进行风险分层和确定治疗靶点。我们假设APOE e4等位基因是SAH后长期残疾的独立危险因素。我们将对所有动脉瘤性蛛网膜下腔出血患者进行前瞻性观察研究，以检验APOE e4等位基因与破裂后3、6和12个月的改良Rankin分级、Barthel指数和一系列神经心理测试结果的关系。在住院期间从常规抽血中获得知情同意后，将获得用于基因分型的血液采集。临床风险因素将使用单变量和多变量统计进行分析。我们将在这个具有严格特征的队列中创建一个DNA库，为未来的基因研究做准备。拟议的项目将利用最繁忙的颅内动脉瘤转诊中心之一，拥有遗传和认知测试方面的专业知识。这项研究将提供有关长期残疾的临床危险因素以及载脂蛋白E在SAH后遗传易感性中的作用的有用信息。识别SAH中APOE的遗传易感性将为研究其他候选基因提供临床模型，这些候选基因可能为未来的治疗策略提供基础。在这个项目中的教学课程和指导计划将建立在候选人的临床培训基础上，并使她发展成为神经血管神经学的独立临床研究员。

DESCRIPTION (provided by applicant): Subarachnoid hemorrhage (SAH) accounts for nearly one-third of potential years of life lost among stroke patients before age 65, with an economic burden estimated at over five billion dollars per year. Prognostic indicators have been unreliable in predicting long-term disability from functional and cognitive impairment. Using genetic predictors like the apolipoprotein E (APOE) genotype will help us with risk stratification and identification of therapeutic targets. We hypothesize that the APOE e4 allele is an independent risk factor for long-term disability after SAH. We will perform a prospective observational study in a cohort of all patients with aneurysmal SAH to examine the relationship between APOE e4 allele and outcome measured by the modified Rankin scale, Barthel Index, and a battery of neuropsychological tests at 3, 6, and 12 months after rupture. Blood collection for genotyping will be obtained after informed consent from routine blood draws during hospitalization. Clinical risk factors will be analyzed using univariate and multivariate statistics. We will create a DNA bank in this rigorously characterized cohort for future genetic studies. The proposed project will take advantage of one of the busiest referral centers for intracranial aneurysms with expertise in genetic and cognitive testing. This research will provide useful information about clinical risk factors for long-term disability and the role of APOE in genetic susceptibility after SAH. Identification of genetic susceptibility from APOE in SAH will provide a clinical model to study other candidate genes that may provide the basis for future treatment strategies. A program of didactic courses and mentoring in this project will build upon the candidate's clinical training, and allow her to develop into an independent clinical investigator in neurovascular neurology.