INvestigations In Gout, Hyperuricemia, and comorbidiTies (INSIGHT) Center of Research Translation (CORT)

项目总结 痛风影响大约4%的美国成年人，是美国最常见的炎症性关节炎 男人。痛风的发病率在全球范围内呈上升趋势，在老年人中可能高达9%。痛风是一种 对医疗保健系统造成重大负担，并与工作效率下降和 生活质量。随着痛风及其相关合并症对人群的影响越来越大， 痛风耀斑的新平移机制及其改善途径的研究 高尿酸血症的结果包括未得到满足的紧急医疗需求。我们的多学科 研究翻译中心对痛风、高尿酸血症和并存疾病(Insight)的调查 (CORT)包括4个研究项目和一个行政核心，其主题是“痛风， 高尿酸血症和相关的合并症“。CORT项目将包括以下研究：确定 创新的外周血白细胞一磷酸腺苷活化蛋白激酶(AMPK)活性 代谢组学有望成为不依赖血清尿酸的痛风发作生物标记物(项目1)，检查 一个互联网案例中关键基因-环境交互作用的影响-痛风发作的交叉研究(项目 2)，揭示了以前报道的全基因组尿酸转运蛋白基因的功能基因组学 联合研究(项目3)，并探讨降尿酸治疗对肾功能的作用机制 在即将开始的痛风治疗比较研究(VA Stop-Gout)中(项目4)。项目范围 从痛风的潜在遗传学和相关炎性病理生物学的基础研究翻译，到 了解痛风慢性肾脏病进展的机制，以及遗传交互作用的翻译 环境因素和药物对精准医学的影响。我们的洞察力CORT旨在： (1)利用独有的优势，实施四个优秀、创新、协同的翻译研究项目 我们三个主要中心的多学科研究团队的优势：阿拉巴马大学伯明翰分校， 哈佛大学和加州大学圣地亚哥分校。(二)培育发展试点和可行性 项目和新的翻译方法的开发和应用，以研究痛风和 高尿酸血症及其相关的主要合并症，特别是慢性肾脏疾病和代谢 综合症。(3)促进对翻译调查人员进行适用于痛风的现行研究方法的培训 通过我们的行政核心监督的浓缩活动来控制高尿酸血症。 -- 洞察力CORT反映了UAB和UAB的专注、相关、多学科的翻译研究计划 合作机构。洞察力CORT组建了一支杰出的科学团队，是独一无二的 准备并坚定地致力于科学严谨、创新和发展新知识和 临床上与NIAMS任务相关的翻译技术。

PROJECT SUMMARY Gout impacts around 4% of the U.S. adult population and is the most common form of inflammatory arthritis in men. The incidence of gout is increasing worldwide and may be as high as 9% in the elderly. Gout is a significant burden on the healthcare system, and is associated with both decreased work productivity and quality of life. With the ever-increasing impact of gout and its associated comorbidities on the population, investigation of novel translational mechanisms mediating gout flares as well as approaches to improving gout and hyperuricemia outcomes comprise an unmet and urgent medical need. Our multi-disciplinary INvestigationS In Gout, Hyperuricemia, and comorbidiTies (INSIGHT) Center of Research Translation (CORT) includes 4 research projects and an Administrative Core focused on the theme, “Gout, Hyperuricemia, and Associated Comorbidities”. CORT projects will include studies to: determine if innovative peripheral blood leukocyte adenosine monophosphate-activated protein kinase (AMPK) activity metabolomics have promise as gout flare biomarkers independent of serum urate (Project 1), examine the influence of key gene-environment interactions within an internet case-crossover study of gout flares (Project 2), unravel the functional genomics of urate transporters genes identified in previously reported genome wide association studies (Project 3), and investigate the mechanism of urate lowering therapy on renal function within the soon to begin comparative study of gout therapies (VA STOP-GOUT) (Project 4). Projects range from basic research translation of underlying genetics and relevant inflammatory pathobiology of gout, to understanding mechanisms of CKD progression in gout, and translation of genetic interaction with environmental factors and medications to precision medicine. Our INSIGHT CORT aims to: (1) Conduct four outstanding, innovative, and synergistic translational research projects drawing on the unique strengths of multidisciplinary research teams at our three major centers: University of Alabama at Birmingham, Harvard University, and University of California San Diego. (2) Foster the development of pilot and feasibility projects and the development and application of new translational methods to research in gout and hyperuricemia and their associated major comorbidities, particularly chronic kidney disease and metabolic syndrome. (3) Promote training of translational investigators in current methods of research applicable to gout and hyperuricemia through enrichment activities overseen by our Administrative Core.   The INSIGHT CORT reflects a focused, relevant, multi-disciplinary translational research program at UAB and partner institutions. The INSIGHT CORT has assembled an outstanding scientific team and is uniquely prepared and strongly committed to scientific rigor, innovation, and development of new knowledge and translational techniques clinically relevant to the mission NIAMS.