Association of poststroke fatigue trajectories with cytokine polymorphims

描述(申请人提供)：在美国，每40秒就有一个人中风。尽管中风后的功能恢复有很大的变数，但中风仍然是导致成人长期残疾的主要原因。随着老龄化人口卒中风险的增加和卒中存活率的增加，提高卒中后的功能恢复至关重要。疲劳是中风后的常见症状。疲劳干扰康复，延迟康复，降低生活质量，并与卒中后较差的功能结局有关。虽然疲劳通常会在中风后3个月内减弱，但许多人会变得持久。为什么这些患者会出现持续性疲劳，目前尚不清楚。我认为，在卒中后3个月和6个月发生的持续性疲劳与炎症风险的增加有关，炎症细胞因子基因的特定遗传多态证明了这一点。为了验证这一假设，我计划进行一项纵向、定量、观察性的研究，评估75名中风后1个月、2个月、3个月和6个月的个体的主观疲劳和整体功能。从口腔细胞中提纯的基因组DNA将用于对影响炎症细胞因子IL-6、IL-12和IL-10表达的启动子基因多态性进行遗传分析。广义线性模型将被用来量化细胞因子多态和中风后疲劳随时间变化的轨迹之间的关系。希望这项研究结果可以支持识别具有更大持续性疲劳风险的个体，并导致开发有针对性的干预措施，以减轻中风后疲劳的负担。除了在遗传和统计技术方面的指导培训外，研究人员还将有人类遗传学、神经学和纵向统计分析方面的额外课程，以确保为成功的研究和学术研究生涯做好充分准备。这项拟议的研究为研究人员开发有针对性的干预措施以改善中风后的功能恢复的长期目标提供了基础。

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.