GENETIC STUDIES OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

动脉瘤性蛛网膜下腔出血的遗传学研究

• 批准号: 2885656
• 负责人: MARK Jay ALBERTS
• 金额: $ 9.24万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2885656
• 关键词: cerebral aneurysm; cerebral hemorrhage; clinical research; elastase inhibitor; elastases; elastin; family genetics; gene mutation; genetic screening; human subject; linkage mapping; stroke; subarachnoid space

Stroke is the third leading cause of death and the leading cause of disability among adults. Recent studies have highlighted the importance of genetic factors in the etiology of several types of stroke. In particular, genetic epidemiologic and molecular genetic studies support the importance of genetic factors in the pathogenesis of familial intracranial aneurysms (IAs) and subarachnoid hemorrhage (SAH). The overall goal of this patient-oriented project is to advance the study of genetic factors responsible for familial IAs and SAH. The primary hypothesis is that specific mutations or susceptibility loci contribute to the development of familial IAs and SAH. Due to the paucity of families with multiple living affecteds having IAs or SAH, a candidate gene approach will be utilized initially. We will focus on genes involved in the metabolism of elastin, based on its importance in vascular integrity and prior studies showing altered elastin, elastase, and elastase inhibitors in patients with IAs and SAH. When adequate family resources are ascertained, genetic linkage studies will be performed. The identification of mutations or genetic susceptibility loci for familial IA/SAH will greatly influence the care of such patients as well as aid the screening and treatment of at-risk asymptomatic family members. This project has a major focus on patient-oriented research. The principal investigator will be involved in the diagnosis and ascertainment of families with IA/SAH. Asymptomatic at-risk family members will be counseled about the need to undergo screening for unruptured IAs using non-invasive techniques such as magnetic resonance angiography and CT angiography. The laboratory based research will focus on screening candidate genes using PCR, SSCP and DNA sequencing techniques. This research project combined with the PI's background and expertise provide a wide range of patient-oriented mentorship opportunities in clinical and genetic research.

中风是成年人死亡的第三大原因，也是导致残疾的主要原因。 最近的研究强调了遗传因素在几种类型中风病因中的重要性。 特别是，遗传流行病学和分子遗传学研究支持遗传因素在家族性颅内动脉瘤（IAs）和 蛛网膜下腔出血（SAH）。 这个以患者为导向的项目的总体目标是推进对家族性 IAs 和 SAH 遗传因素的研究。 主要假设是 特定突变或易感位点有助于家族性 IAs 和 SAH 的发生。 由于患有 IAs 或 SAH 的家庭很少，因此最初将采用候选基因方法。 我们将重点关注参与弹性蛋白代谢的基因，因为它对血管完整性的重要性以及先前的研究显示 IAs 和 SAH 患者中弹性蛋白、弹性蛋白酶和弹性蛋白酶抑制剂发生了改变。 当家庭资源充足时 确定后，将进行遗传连锁研究。 家族性IA/SAH突变或遗传易感位点的鉴定将极大地影响此类患者的护理，并有助于筛查和治疗高危无症状家庭成员。 该项目主要侧重于以患者为导向的研究。 主要研究者将参与 IA/SAH 家庭的诊断和确定。 无症状高危人群 将告知家庭成员是否需要使用磁共振血管造影和 CT 血管造影等非侵入性技术对未破裂的 IAs 进行筛查。 这 基于实验室的研究将侧重于使用 PCR、SSCP 和 DNA 测序技术筛选候选基因。 该研究项目结合了 PI 的背景和专业知识，为临床和基因研究提供了广泛的以患者为导向的指导机会。