Project 2: Novel Risk Factors and Precision Medicine for Gout Flares

项目 2：痛风发作的新危险因素和精准医学

• 批准号: 10017005
• 负责人: HYON K CHOI
• 金额: $ 25.41万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017005
• 关键词: ABCG2 gene; Address; Adult; Affect; Alcohol consumption; Allopurinol; Arthritis; Boston; Caring; Cessation of life; Chronic Kidney Failure; Clinical; Coffee; Data; Databases; Diet; Diuretics; Fibrinogen; Flare; Fructose; Genes; Genetic; Genomics; Goals; Gout; Guidelines; High Prevalence; Hypertension; Hyperuricemia; IGF1R gene; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Arthritis; Intake; Intervention; Investigation; Life Style; Measures; Metabolism; PRKAG2 gene; Pain; Pathogenesis; Patient Education; Patients; Pharmaceutical Preparations; Pharmacogenomics; Pharmacology; Prevalence; Purines; Race; Recurrence; Registries; Research; Research Design; Rheumatology; Risk; Risk Factors; Role; Series; Serum; Subgroup; Targeted Research; Tea; Therapeutic; Time; Translating; Translational Research; Urate; Variant; biobank; clinical efficacy; clinical practice; cohort; comorbidity; cost effective; evidence base; experience; genome wide association study; innovation; modifiable risk; novel; personalized approach; precision medicine; premature; risk variant; soft drink; sugar; sweetened beverage

PROJECT SUMMARY 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.

项目总结