Gout affects ~1 to 2% of the U.S. population. With an aging population, the societal burden of gout will likely grow. The role of genetic factors on gout and hyperuricemia among different races/ethnicities and the mechanisms by which treatment of hyperuricemia may impact vascular disease remain poorly understood. While the causes of hyperuricemia are known, and efficacious treatments for gout are available, there are large gaps in the quality of care of gout patients. These care gaps, the societal impact of gout, and rising concerns about deleterious effects of hyperuricemia make these conditions ideal targets for translational research. Our multi-disciplinary UAB CORT includes 4 research projects and an administrative core focused on the theme of """"""""Gout and Hyperuricemia: from Bench to Bedside to Backyard. Gout, hyperuricemia, and vascular disease are more common among African Americans than Caucasians, yet little is known about genetic and environmental factors associated with increased risk of gout in this minority population. Our four projects are thus further united by a sub-theme of racial/ethnic disparities in gout and hyperuricemia. We will analyze the association of gout and hyperuricemia with cardiovascular disease in African-Americans and define genetic variants and environmental and medical factors underlying hyperuricemia and gout in this minority group (Project 1);characterize biomarkers of inflammation (CRP), vascular disease (endothelial function), and blood pressure changes associated with the ULT allopurinol (Project 2);examine factors associated with suboptimal gout care and factors influencing effective and safer dosing of allopurinol and colchicine in African-Americans and Caucasians (Project 3);and compare the effectiveness of a novel pharmacy-based """"""""virtual"""""""" Gout Clinic that includes protocol-driven care to usual care in the treatment of chronic gout (Project 4). The overall goal of our CORT is to improve the health of patients with gout and hyperuricemia by applying scientifically rigorous, state-of-the-art methodology to clinically important questions in translational investigation and to educate clinical investigators through an enrichment program. Drawing on the unique strengths of many UAB Centers, Departments, and Programs, and in collaboration with an experienced team of 20 investigators representing 5 disciplines, our innovative projects hold the promise of significant improvements in our understanding of the pathogenesis of gout, hyperuricemia, and related co-morbid conditions, and may ultimately lead to better ways to predict, treat, or prevent gout and hyperuricemia.

Public Health Relevance

Gout and high serum urate levels are common in the general population, as are associated conditions such as cardiovascular disease. A better understanding of the genetic and environmental influences on gout, and hyperuricemia in different races/ethnicities would ultimately improve public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR060772-02
Application #
8525343
Study Section
Special Emphasis Panel (ZAR1-KM (M1))
Program Officer
Witter, James
Project Start
2012-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$1,089,209
Indirect Cost
$231,382
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

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