Association of poststroke fatigue trajectories with cytokine polymorphims

中风后疲劳轨迹与细胞因子多态性的关联

• 批准号: 8452235
• 负责人: Kristianna Baldwin Weymann
• 金额: $ 3万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8452235
• 关键词: Adult; Affect; Animal Model; Anxiety; Brain Injuries; Cells; Chronic; Clinical Research; Cross-Sectional Studies; Cytokine Gene; DNA; Data; Development; Disease; Distress; Early identification; Education; Electrophoresis; Enrollment; Ensure; Equipment and supply inventories; Family; Fatigue; Foundations; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Growth; Hospitals; Human Genetics; Individual; Inflammation; Inflammatory; Inflammatory Response; Interleukin-1; Interleukin-10; Interleukin-12; Interleukin-6; Intervention; Knowledge; Lead; Light; Linear Models; Measures; Mental Depression; Mentors; Methods; Modeling; Neurology; Observational Study; Participant; Patients; Pattern; Peripheral; Play; Polymerase Chain Reaction; Preparation; Production; Publishing; Quality of life; Recovery; Recovery of Function; Recruitment Activity; Rehabilitation therapy; Research; Research Personnel; Research Proposals; Research Support; Risk; Role; Stroke; Survivors; Symptoms; Techniques; Testing; Time; Training; United States; aging population; base; career; cytokine; disability; experience; functional outcomes; genetic analysis; improved; indexing; interest; neurological recovery; post stroke; prevent; primary outcome; promoter; stroke recovery; therapy development

DESCRIPTION (provided by applicant): Every 40 seconds, someone in the United States has a stroke. Although functional recovery from stroke is quite variable, stroke continues to be the leading cause of long-term adult disability. With an aging population at increased risk of stroke and increased survival from stroke, improving functional recovery from stroke is critically important. Fatigue is a common symptom following stroke. Fatigue interferes with rehabilitation, delays recovery, decreases quality of life, and is associated with worse functional outcomes after stroke. Although fatigue generally declines within 3 months of stroke in many it can become persistent. Why persistent fatigue occurs in these patients is unclear. I propose that persistent fatigue that occurs in individuals at 3 and 6 months after stroke is related to an elevated inflammatory risk as evidenced by specific genetic polymorphisms in inflammatory cytokine genes. To test this hypothesis I plan to conduct a longitudinal, quantitative, observational study, to assess subjective fatigue and overall function in 75 individuals 1-, 2-, 3- and 6 months post stroke. Genomic DNA purified from buccal cells will be used to perform genetic analysis of promoter polymorphisms that affect expression of the inflammatory cytokines, interleukin (IL)-6, IL-12, and IL-10. Generalized linear modeling will be used to quantify associations between cytokine polymorphisms and trajectories of poststroke fatigue over time. It is hoped that study findings may support the identification of individuals at greates risk of persistent fatigue and lead to the development of targeted interventions to reduce the burden of poststroke fatigue. The investigator will have additional coursework in human genetics, neurology, and longitudinal statistical analysis, in addition to mentored training in genetic and statistical techniques to ensure adequate preparation for a successful study and an academic research career. The proposed research provides a foundation for the investigator's long-term goal to develop targeted interventions to improve functional recovery from stroke.

描述（由申请人提供）：每40秒，美国就有一人中风。尽管中风的功能恢复差异很大，但中风仍然是成人长期残疾的主要原因。随着老龄化人群卒中风险增加和卒中生存率增加，改善卒中功能恢复至关重要。疲劳是中风后的常见症状。疲劳干扰康复，延迟恢复，降低生活质量，并与卒中后更差的功能结局相关。虽然疲劳通常在中风后3个月内下降，但在许多情况下，它可能会变得持久。为什么这些患者会出现持续性疲劳尚不清楚。我认为，持续性疲劳发生在个人在3个月和6个月后中风是与炎症风险升高的炎症细胞因子基因的特定遗传多态性所证明的。为了验证这一假设，我计划进行一项纵向、定量、观察性研究，以评估75名卒中后1、2、3和6个月的患者的主观疲劳和整体功能。将使用从口腔细胞纯化的基因组DNA对影响炎性细胞因子白细胞介素（IL）-6、IL-12和IL-10表达的启动子多态性进行遗传分析。广义线性模型将用于量化细胞因子多态性与卒中后疲劳随时间推移的轨迹之间的关联。希望研究结果可以支持识别持续性疲劳风险最高的个体，并导致有针对性的干预措施的发展，以减少中风后疲劳的负担。研究者将有人类遗传学，神经学和纵向统计分析的额外课程，除了遗传和统计技术的指导培训，以确保为成功的研究和学术研究生涯做好充分的准备。拟议的研究为研究者的长期目标提供了基础，即开发有针对性的干预措施，以改善中风后的功能恢复。