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.

Public Health Relevance

Gout and its associated comorbidities cause a significant societal burden. 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?. The overall goal for the INSIGHT CORT is to conduct scientifically rigorous state of the art translational research aimed at unraveling molecular mechanisms and improving the precision of care in gout and hyperuricemia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
2P50AR060772-06
Application #
9370388
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Witter, James
Project Start
2012-09-20
Project End
2022-08-31
Budget Start
2017-09-20
Budget End
2018-08-31
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Ryan, Evan M; Duryee, Michael J; Hollins, Andrew et al. (2018) Antioxidant properties of citric acid interfere with the uricase-based measurement of circulating uric acid. J Pharm Biomed Anal 164:460-466
Melles, Ronald B; Jorge, April M; Marmor, Michael F et al. (2018) Sharp decline in hydroxychloroquine dosing-analysis of 17,797 initiators from 2007 to 2016. Clin Rheumatol 37:1853-1859
Bursill, David; Taylor, William J; Terkeltaub, Robert et al. (2018) Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions for disease elements in gout. Arthritis Care Res (Hoboken) :
Jorge, April; Wallace, Zachary S; Zhang, Yuqing et al. (2018) All-Cause and Cause-Specific Mortality Trends of End-Stage Renal Disease due to Lupus Nephritis from 1995 to 2014. Arthritis Rheumatol :
Choi, Hyon; Neogi, Tuhina; Stamp, Lisa et al. (2018) New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert. Arthritis Rheumatol 70:1702-1709
McWherter, Charles; Choi, Yun-Jung; Serrano, Ramon L et al. (2018) Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. Arthritis Res Ther 20:204
Sun, Mengying; Vazquez, Ana I; Reynolds, Richard J et al. (2018) Untangling the complex relationships between incident gout risk, serum urate, and its comorbidities. Arthritis Res Ther 20:90
Mikuls, Ted R; Cheetham, T Craig; Levy, Gerald D et al. (2018) A Pharmacist-Led Intervention to Improve Gout Medication Adherence and Outcomes with Urate Lowering Therapy: A Site Randomized Trial. Am J Med :
Johnson, Tate M; Register, Kyle A; Schmidt, Cynthia M et al. (2018) Correlation of the Multi-Biomarker Disease Activity Score with Rheumatoid Arthritis Disease Activity Measures: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken) :
England, Bryant R; Thiele, Geoffrey M; Anderson, Daniel R et al. (2018) Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ 361:k1036

Showing the most recent 10 out of 57 publications