Association of poststroke fatigue trajectories with cytokine polymorphims

描述（由申请人提供）：在美国，每40秒就有一人中风。虽然中风后的功能恢复非常不稳定，但中风仍然是导致成人长期残疾的主要原因。随着人口老龄化，卒中风险增加，卒中生存率提高，改善卒中后功能恢复至关重要。疲劳是中风后的常见症状。疲劳干扰康复，延缓恢复，降低生活质量，并与卒中后更差的功能预后相关。虽然疲劳通常在中风后3个月内减轻，但对许多人来说，疲劳可能会持续下去。这些患者出现持续性疲劳的原因尚不清楚。我认为，在中风后3至6个月出现的持续性疲劳与炎症风险升高有关，炎症细胞因子基因的特定遗传多态性证明了这一点。为了验证这一假设，我计划进行一项纵向、定量、观察性研究，以评估75名患者中风后1、2、3和6个月的主观疲劳和整体功能。从颊细胞中纯化的基因组DNA将用于对影响炎症细胞因子、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脑卒中后疲劳轨迹之间的关系。希望研究结果可以支持识别持续性疲劳风险较高的个体，并导致有针对性的干预措施的发展，以减轻中风后疲劳的负担。研究者除了在遗传和统计技术方面的指导培训外，还将学习人类遗传学、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的准备。提出的研究为研究者制定有针对性的干预措施以改善中风后功能恢复的长期目标奠定了基础。

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.