Apolipoprotein E and Outcomes in Subarachnoid Hemorrhage

描述（由申请人提供）：在65岁之前中风患者中，蛛网膜下腔出血（SAH）占潜在寿命损失年数的近三分之一，每年造成的经济负担估计超过50亿美元。预后指标在预测功能和认知损伤引起的长期残疾方面并不可靠。使用载脂蛋白E （APOE）基因型等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SAH患者进行一项前瞻性观察性研究，以检查APOE e4等位基因与预后之间的关系，这些预后通过改良Rankin量表、Barthel指数和一系列神经心理学测试在破裂后3、6和12个月测量。在获得住院期间常规抽血的知情同意后，采集血液进行基因分型。临床危险因素将采用单因素和多因素统计分析。我们将在这个严格特征的队列中创建一个DNA库，用于未来的遗传研究。拟议中的项目将利用最繁忙的颅内动脉瘤转诊中心之一，在遗传和认知测试方面具有专业知识。这项研究将为SAH后长期残疾的临床危险因素和APOE在遗传易感性中的作用提供有用的信息。确定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，这些基因可能为未来的治疗策略提供基础。在这个项目中，教学课程和指导计划将建立在候选人的临床培训基础上，使她能够发展成为一名独立的神经血管神经学临床研究者。

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.