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上升。痛风严重负担医疗保健系统， 与工作效率和生活质量下降有关。随着痛风的影响越来越大 及其对人群的相关合并症，研究新的翻译机制介导 痛风发作以及改善痛风和高尿酸血症结果的方法包括未满足的， 紧急医疗需求。当获得资助时，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个活跃的研究项目和一个 行政核心关注的主题是“痛风、高尿酸血症和相关合并症”。 项目包括研究：确定腺苷一磷酸活化蛋白激酶（AMPK）活性 代谢组学有希望作为不依赖于血清尿酸盐（P1）的痛风生物标志物， 痛风发作（P2）互联网研究中的关键基因-环境相互作用，揭示了功能基因组学 在先前报道的全基因组关联研究中鉴定的尿酸盐转运蛋白基因（P3），以及 探讨VA STOP-GOUT（P4）患者降尿酸治疗对肾功能影响的机制。项目 范围从基础研究翻译的潜在遗传学和炎症病理学的痛风， 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。拟议的修订项目（P5）旨在 利用一种新的急诊科为基础的干预测试方法，以改善护理痛风患者， 第二个目标是同时加强少数群体对研究的参与。的 修订后的INSIGHT CORT旨在：（1）开展五个杰出的、创新的和协同的研究项目 利用我们四个主要中心多学科研究团队的独特优势： 伯明翰的亚拉巴马、哈佛大学、加州圣地亚哥大学，现在是范德比尔特大学 （2）促进试点项目和可行性项目的发展， 新的翻译方法在痛风和高尿酸血症及其相关疾病研究中的应用 合并症，特别是CKD和代谢综合征;（3）促进翻译研究者的培训 在目前适用于痛风和高尿酸血症的研究方法中， 我们的行政核心通过患者入组，拟定翻修项目与CORT直接相关 痛风CORT登记和生物储存库，为项目提供临床数据和生物样本。 INSIGHT CORT是UAB和合作机构的多学科转化研究计划。我们 组建了一支优秀的团队，并做好了独特的准备，并坚定地致力于科学严谨， 创新，知识和翻译技术的发展。

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. Gout significantly burdens 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. When funded, the INvestigationS In Gout, Hyperuricemia, and comorbidiTies (INSIGHT) Center of Research Translation (CORT) included 4 active research projects and an Administrative Core focused on the theme, “Gout, Hyperuricemia, and Associated Comorbidities”. Projects include studies to: determine if adenosine monophosphate-activated protein kinase (AMPK) activity metabolomics have promise as gout biomarkers independent of serum urate (P1), examine the influence of key gene-environment interactions within an internet study of gout flares (P2), unravel the functional genomics of urate transporter genes identified in previously reported genome wide association studies (P3), and investigate the mechanism of urate lowering therapy on renal function within VA STOP-GOUT (P4). Projects range from basic research translation of underlying genetics and 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. The proposed revision project (P5) aims to utilize a novel emergency department based intervention to test methods to improve the care gout patients in the Deep South, with a secondary goal of concurrently enhancing participation of minorities in research. The revised INSIGHT CORT aims to: (1) Conduct five outstanding, innovative, and synergistic research projects drawing on the unique strengths of multidisciplinary research teams at our four major centers: University of Alabama at Birmingham, Harvard University, University of California San Diego, and now Vanderbilt University Medical Center; (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 CKD and metabolic syndrome; and (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 proposed revision project directly ties to the CORT through patient enrollment into the Gout CORT Registry and Biorepository, which contributes clinical data and biological samples to projects. The INSIGHT CORT is a multi-disciplinary translational research program at UAB and partner institutions. We have assembled an outstanding team and are uniquely prepared and strongly committed to scientific rigor, innovation, and development of knowledge and translational techniques.