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

项目摘要 痛风影响约4%的美国成年人口，是美国最常见的炎性关节炎。 男人痛风的发病率在全球范围内不断增加，在老年人中可能高达9%。痛风是一 对医疗保健系统造成重大负担，并与工作效率降低和 生活质量随着痛风及其相关合并症对人群的影响不断增加， 研究新的翻译机制介导痛风发作以及改善痛风的方法 并且高尿酸血症的结果包括未满足的和紧急的医疗需求。我们的多学科 痛风、高尿酸血症和合并症的研究（INSIGHT）研究翻译中心 （CORT）包括4个研究项目和一个行政核心，重点是“痛风， 高尿酸血症及相关合并症”。CORT项目将包括以下研究： 创新外周血白细胞腺苷一磷酸活化蛋白激酶（AMPK）活性 代谢组学有希望作为痛风发作的生物标志物独立于血清尿酸盐（项目1），检查 痛风发作互联网病例交叉研究中关键基因-环境相互作用的影响 2），解开以前报道的全基因组中鉴定的尿酸盐转运蛋白基因的功能基因组学 相关研究（项目3），并探讨降尿酸治疗对肾功能的作用机制 即将开始的痛风治疗比较研究（VA STOP-GOUT）（项目4）。项目范围 从基础研究翻译潜在的遗传学和相关的炎症病理学的痛风， 了解痛风中CKD进展的机制，以及与 从环境因素和药物到精准医疗。我们的INSIGHT CORT旨在： (1)进行四个杰出的，创新的，协同的转化研究项目，利用独特的 我们三大中心的多学科研究团队的优势：亚拉巴马大学伯明翰分校， 哈佛大学和加州圣地亚哥大学。(2)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 综合征(3)促进翻译研究人员在当前适用于痛风的研究方法方面的培训 和高尿酸血症通过丰富的活动由我们的行政核心监督。 INSIGHT CORT反映了UAB的重点，相关，多学科的翻译研究计划， 伙伴机构。INSIGHT CORT汇集了一支优秀的科学团队， 准备并坚定地致力于科学严谨，创新和新知识的发展， 与NIAMS使命临床相关的翻译技术。

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.