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

项目摘要 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。痛风的发病率在世界范围内呈上升趋势。痛风给医疗系统带来了沉重的负担，而且 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 及其在种群上的相关共病，新的翻译机制的研究 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和 紧急医疗需要。当被资助时，痛风、高尿酸血症和合并症的调查 (洞察)研究翻译中心(CORT)包括4个正在进行的研究项目和一个 行政核心侧重于“痛风、高尿酸血症和相关的合并症”这一主题。 项目包括：确定一磷酸腺苷活化蛋白激酶(AMPK)的活性 代谢组学有望成为独立于血清尿酸(P1)的痛风生物标志物，检查 痛风发作互联网研究中的关键基因-环境相互作用(P2)，揭开功能基因组学的面纱 先前报道的全基因组关联研究中发现的尿酸转运蛋白基因(P3)，以及 探讨降尿酸治疗对痛风患者肾功能的影响机制。项目 范围从痛风的潜在遗传学和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，到精准医学。拟议的修订项目(P5)旨在 利用以急诊科为基础的新型干预措施来测试改善痛风患者护理的方法 南方腹地，次要目标是同时加强少数群体对研究的参与。这个 修订后的洞察力CORT的目标是：(1)进行五个杰出的、创新的和协同的研究项目 利用我们四个主要中心的多学科研究团队的独特优势： 阿拉巴马州伯明翰大学、哈佛大学、加州大学圣地亚哥分校，现在是范德比尔特大学 医疗中心；(2)促进试点和可行性项目的发展，以及 新的翻译方法在痛风、高尿酸血症及其相关专业研究中的应用 合并症，特别是慢性肾脏病和代谢综合征；以及(3)促进翻译研究人员的培训 在目前适用于痛风和高尿酸血症的研究方法中，通过由 我们的行政核心。拟议的修订项目通过患者登记直接与CORT挂钩 痛风皮肤病注册和生物库，为项目提供临床数据和生物样本。 洞察力CORT是UAB及其合作机构的一个多学科翻译研究项目。我们 组建了一支出色的团队，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.