Gout is a common and excruciatingly painful inflammatory arthritis associated with hyperuricemia. The prevalence of gout has increased over the past few decades to 3.9% of US adults (8.3 million individuals), which is further complicated by a high level of comorbidities (CoRT theme, including chronic kidney disease (CKD)) and their sequelae (e.g., premature death). Despite our understanding of gout's pathogenesis and available medications, gout management remains suboptimal with recurrent attacks occurring frequently, and there is a clear need to broaden the evidence-based and personalized precision approach to gout care. Our previous Boston Online Gout Study successfully provided the relevant evidence about the role of traditionally purported risk factors for gout flares in pre-existing gout patients, which was endorsed by the latest ACR gout guidelines. However, evidence for purported novel common modifiable risk factors as well as genetic and other key attributes, which are essential for precision gout care, are lacking. To fill this key evidence gap, we will expand our successful platform of the Boston Online Gout Study by following 800 gout patients from the Partners Biobank cohort (N >75,000) and 200 black gout patients from the UAB Rheumatology Arthritis Database and Registry over the course of 1 year. We will first examine novel common modifiable factors (i.e., sugar-sweetened beverages, coffee, and tea) for the risk of gout flares (Aim 1). Furthermore, we will translate recent genomic research data towards precision medicine in gout care for both lifestyle and pharmacologic interventions. Specifically, we will examine the purported influence of urate genes involved in sugar transport (SLC2A9) and metabolism genes (GCKR, IGF1R, and INHBB) on the impact of key risk factors for gout flares (Aim 2). We will also examine the purported impact of the ABCG2 variant (Q141K) and PRKAG2 variant (which encodes the gamma chain of AMPK (a master regulator of gouty inflammation)) on allopurinol's clinical efficacy for gout flares, as well as the purported role of the SLC2A9 variant on diuretic-induced gout flares (Aim 3). Finally, we will examine the role of other key attributes (i.e., race (black) and CKD status (stage 3 or higher)) on the impact of key triggers of gout flares among gout patients to further precision gout care (Aim 4).
These aims address novel, common risk factors, gene-environmental interactions, pharmacogenomics, and race/CKD impact, all of which can be readily translated into clinical practice to optimize gout care. Further, the innovative and cost-effective study design leverages our group's extensive gout research experience and provides key research translation for precision medicine in gout. This project will have an important positive impact on millions of gout patients by filling key evidence gaps on modifiable factors and relevant subgroups at risk for gout flares.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR060772-07
Application #
9568313
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
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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