Risk Factors For Gout Research Articles

Carbon dots modified hydrange-shaped ZnCo(OH)F used as a flexible electrode for sensitive detection of dopamine and uric acid

Dopamine (DA), widely recognized as the most prevalent catecholamine neurotransmitter in the brain, functions as a vital regulator of various physiological processes within the central nervous system. Meanwhile, uric acid (UA) serves as the terminal product of purine metabolism, and hyperuricemia emerges as a significant risk factor for gout, with a steep escalation in risk as blood uric acid levels surge. Consequently, monitoring the concentrations of DA and UA in biological fluids is crucial not only for the treatment of related disorders but also for enhancing disease prevention strategies. In this work, the blooming hydrangea shaped ZnCo(OH)F/carbon dots (CDs) composite was grown on carbon cloth (CC) substrate by a simple hydrothermal method, which was used as a flexible sensor for the detection of DA and UA. The unique open structure and morphologic adjustment strategy of ZnCo(OH)F/CDs/CC provided a large surface area and highly exposed active site. After screening the experimental variables that affect the sensor performance, the optimal ZnCo(OH)F/CDs/CC flexible electrode achieved individual and simultaneous detection for DA and UA in the concentration ranges of 1.0220.0µM and 1.0500.0µM, the detection limits (LOD) of DA and UA were 0.0129 and 0.044μM, respectively (S/N=3). In addition, the sensor exhibited good repeatability, stability and selectivity, realizing the detection of DA and UA in human serum with recovery rate of 95.20% 105.3%. Also, the density functional theory (DFT) calculations were used to explore the interaction between electrode material and detected substrate. A simple hydrothermal method was utilized to grow the ZnCo(OH)F/CDs composite onto the CC substrate. The presence of F− in ZnCo(OH)F can increase the charge mobility and improve the conductivity. ZnCo(OH)F/CDs/CC as flexible electrode material can determine DA and UA simultaneously in human serum with a satisfactory recovery rate. This flexible sensor has a broad application prospect in the manufacture of wearable devices.

Incidence and Risk Factors of Gout in Nondialysis-Dependent Patients with CKD and Asymptomatic Hyperuricemia

Incidence and Risk Factors of Gout in Nondialysis-Dependent Patients with CKD and Asymptomatic Hyperuricemia

The effect of exercise rehabilitation with exergames combined with ice therapy in the treatment of obese patients with gout: protocol for a clinical trial

BackgroundGout remains a leading cause of inflammatory arthritis worldwide, and the main risk factor for gout is persistent hyperuricemia. The clinical management of gout is mostly drug-based, and other treatment options are often ignored. This research proposal will explore whether exergames combined with ice therapy can help patients with gout to lose weight, relieve pain, improve the range of movement, improve quality of life, decrease uric acid level, decrease kinesiophobia and improve mental health of patients with gout.MethodsThis experiment will use a two-arm randomized controlled design. The study setting is at the Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM). Obese patients with gout (N = 30) will be randomly assigned to the control group (receive an exergames intervention) and intervention group (receive an exergames intervention combined with ice therapy). The outcomes measurement will be conducted before (baseline) and after intervention (4 weeks). Then, it will be followed up at 12 weeks.DiscussionTo our knowledge, no study has investigated the effect of exergames and ice therapy among gout patients. This study is expected to demonstrate that exercise rehabilitation facilitated by exergames with ice therapy is more effective in gout management compared to a conventional rehabilitation intervention.Trial registrationChinese Clinical Trial Registry (ChiCTR2300070029). Registered on 31 March 2023.

Current updates for hyperuricemia and gout in age-related macular degeneration.

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

Meta-analysis and systematic review of gout prevalence in the heart/lung transplantation population.

Gout may complicate solid organ transplantation with potentially serious consequences. An accurate prevalence of gout in this population is unknown. This study aimed to estimate the prevalence of gout in the heart and/or lung transplantation population through a systematic review and meta-analysis. MEDLINE, Embase, PsycINFO, CENTRAL and Cochrane Library (inception to February 2022) were searched for studies that reported the prevalence and/or incidence of gout in heart and/or lung transplant recipients. Two authors extracted outcomes data. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were the prevalence of pre- or post-transplant gout expressed as a prevalence rate (95% CI). Secondary outcomes included risk factors for gout, adverse events, and therapeutic complications of gout treatment. Ten studies were included. Gout prevalence (PR) was 8% pre-transplant (PR = 0.08; 95% CI: 0.05-0.12; 4 studies n = 651) and 6% post-transplant (PR = 0.06; 95% CI: 0.06-0.06; 10 studies n = 45,298). Post-transplant gout prevalence in heart transplant recipients was almost three times higher than lung transplant recipients (PR = 0.16; 95% CI: 0.13-0.20 vs. PR = 0.06; 95% CI: 0.05-0.06 respectively). Patients with a pre-transplant history of gout had a higher risk of developing post-transplant gout than patients without (RR = 3.61; 95% CI: 2.19-5.95). Factors associated with gout and outcomes for heart and/or lung transplant recipients with gout were comprehensively reviewed from the included studies. Gout is highly prevalent in heart and/or lung transplant patients. Pre-transplant gout is predictive of developing symptomatic post-transplant gout. This has significant implications for management of heart/lung transplant patients. https://www.crd.york.ac.uk/, PROSPERO (CRD42020190632).

Large-scale cross-ancestry genome-wide meta-analysis of serum urate

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.

Identification of potential biomarkers of gout through weighted gene correlation network analysis.

Although hyperuricemia is not always associated with acute gouty arthritis, uric acid is a significant risk factor for gout. Therefore, we investigated the specific mechanism of uric acid activity. Using the gout-associated transcriptome dataset GSE160170, we conducted differential expression analysis to identify differentially expressed genes (DEGs). Moreover, we discovered highly linked gene modules using weighted gene coexpression network analysis (WGCNA) and evaluated their intersection. Subsequently, we screened for relevant biomarkers using the cytoHubba and Mcode algorithms in the STRING database, investigated their connection to immune cells and constructed a competitive endogenous RNA (ceRNA) network to identify upstream miRNAs and lncRNAs. We also collected PBMCs from acute gouty arthritis patients and healthy individuals and constructed a THP-1 cell gout inflammatory model, RT-qPCR and western blotting (WB) were used to detect the expression of C-X-C motif ligand 8 (CXCL8), C-X-C motif ligand 2 (CXCL2), and C-X-C motif ligand 1 (CXCL1). Finally, we predicted relevant drug targets through hub genes, hoping to find better treatments. According to differential expression analysis, there were 76 upregulated and 28 downregulated mRNAs in GSE160170. Additionally, WGCNA showed that the turquoise module was most strongly correlated with primary gout; 86 hub genes were eventually obtained upon intersection. IL1β, IL6, CXCL8, CXCL1, and CXCL2 are the principal hub genes of the protein-protein interaction (PPI) network. Using RT-qPCR and WB, we found that there were significant differences in the expression levels of CXCL8, CXCL1, and CXCL2 between the gouty group and the healthy group, and we also predicted 10 chemicals related to these proteins. In this study, we screened and validated essential genes using a variety of bioinformatics tools to generate novel ideas for the diagnosis and treatment of gout.

Gout: physical activity in therapy and prevention of the disease

Gout is a systemic chronic inflammatory disease associated with purine metabolism disorders. Risk factors for gout are a combination of genetic and environmental factors. Taking into account such features of the pathogenesis of gout as hyperuricemia and the deposition of monosodium urate crystals in tissues and joints, the development of the inflammatory, researchers studied the effect of physical activity on its main links. The intensity of the load and the type of physical exercise were taken into account due to their possible effect on metabolic processes. There is currently no reliable evidence on the importance of physical activity in reducing serum uric acid levels. Research has shown that physical activity has a positive effect on inflammation between gout attacks. The use of physical exercise can indirectly affect uric acid levels by reducing body weight in comorbid pathologies. EULAR emphasizes physical activity to prevent cardiovascular risks, which is also important for gout. Conclusions. Physical activity as one of the components of lifestyle is important for gout due to its effect on the inflammatory process and the prevention of relapses, a general strengthening effect on the body, an effect on hyperuricemia due to the positive effect associated with comorbid pathology, and a decrease in cardiovascular risk and associated him premature death. Physical activity of low and moderate intensity is effective for gout. Preference is given to aerobic exercise, taking into account the nature of metabolism and the possible impact on the occurrence of gout attacks. Further study and development of the characteristics of physical activity in gout are necessary to improve the prevention and treatment of the disease, and the development of individual recommendations for patients (for the management of gout).

Global burden and epidemic trends of gout attributable to high body mass index from 1990 to 2019.

Gout is an inflammatory and metabolic disease characterized by arthritis and elevation of the serum uric acid (SUA) level. More and more studies have shown that high body mass index (BMI) has become one of the most important risk factors for gout. We used the data of gout burden attributed to high body mass index (BMI) from global burden of disease (GBD) study 2019 to provide insights for reducing the global burden of gout. From 1990 to 2019, the prevalence and DALYs of gout caused by high BMI worldwide has been increasing. The burden of gout caused by high BMI is heavier in the elderly male group and regions with high SDI worldwide. Our findings provide evidence for the burden of gout caused by high BMI. Developing a weight management plan and lifestyle habits for groups severely affected by gout will effectively reduce the global disease and economic burden.

Relieving urinary tract obstructions may increase the risk of gouty arthritis in patients with hyperuricemia and postrenal obstructions.

To evaluate the effect of relieving urinary tract obstructions (RUO) on the risk of gouty arthritis in patients with postrenal obstructions and hyperuricemia. We retrospectively analyzed the clinical data of 130 patients with urinary tract obstructions at Rongcheng People's Hospital from 2018 to 2021. Patients were divided into groups A (n = 62) and B (n = 68) according to the treatment method. Patients in group A underwent conservative treatments, such as drugs, extracorporeal shock wave lithotripsy (ESWL), and hemodialysis. Patients in Group B underwent catheterization, cystostomy, nephrostomy, or double J ureteral catheterization for rapid RUO. The ages of groups A and B were 58.40 ± 17.69 and 59.63 ± 16.12 years, respectively (P = .42). Before treatment, the serum uric acid values were 572.05 ± 106.93 and 567.79 ± 97.21 µmol/L, respectively (P = .94); serum creatinine values were 226.66 ± 269.67 and 280.15 ± 200.75 µmol/L, respectively (P = .88); and urine volumes were 913.23 ± 481.92 and 886.18 ± 552.72 mL/24 h, respectively (P = .08). No significant differences in the general data were identified between the two groups (P > .05). The effects of the two treatments on the incidence of gout in patients with hyperuricemia complicated by postrenal obstruction were compared based on changes in uric acid level, creatinine level, and urine volume within 1 week after treatment. Multivariate logistic regression analysis was used to analyze clinical factors that increased the incidence of gout after RUO. The gout incidence rates in group A before and after treatment were 8.1% (5/62) and 6.5% (4/62), respectively (P > .99). The gout incidence rates in group B before and after treatment were 4.4% (3/68) and 19.1% (10/68), respectively (P = .01). Group B had a statistically significant increase in the gout incidence rate after RUO (P < .05). Multivariate logistic regression analysis showed that having an age > 60 years, urine volume ≤400 mL/24 h, and creatinine level > 186 µmol/L before treatment were risk factors for gout in patients with hyperuricemia after RUO. Relieving urinary tract obstruction increases the risk of gouty arthritis in patients with hyperuricemia and acute postrenal obstruction. Age, urine volume, and creatinine levels before treatment are risk factors for gout in patients with hyperuricemia after RUO.

The relationship between education attainment and gout, and the mediating role of modifiable risk factors: a Mendelian randomization study.

To investigate the causal relationship between educational attainment (EA) and gout, as well as the potential mediating effects of individual physical status (IPS) such as body mass index (BMI) and systolic blood pressure (SBP) and lifestyle habits (LH) including alcohol intake frequency (drinking), current tobacco smoking (smoking), and time spent watching television (TV). Utilizing two-sample Mendelian randomization (MR), we analyzed the causal effects of EA on gout risk, and of IPS (BMI and SBP) and LH (smoking, drinking, and TV time) on gout risk. Multivariable MR (MVMR) was employed to explore and quantify the mediating effects of IPS and LH on the causal relationship between EA and gout risk. An elevation of educational attainment by one standard deviation (4.2 years) exhibited a protective effect against gout (odds ratio 0.724, 95% confidence interval 0.552-0.950; p = 0.020). We did not observe a causal relationship between smoking and gout, but BMI, SBP, drinking, and TV time were found to be causal risk factors for gout. Moreover, BMI, SBP, drinking, and TV time acted as mediating factors in the causal relationship between EA and gout risk, explaining 27.17, 14.83, 51.33, and 1.10% of the causal effects, respectively. Our study indicates that having a genetically predicted higher level of EA may provide protection against gout. We found that this relationship is influenced by IPS factors such as BMI and SBP, as well as LH including drinking and TV time.

Lower plasma linoleic acids as a risk factor for gout: an integrated analysis of population-based cohort and genetic data.

Background: Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method: We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs (% total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results: Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P-trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P-trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions: Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

Epidemiology of gout - Global burden of disease research from 1990 to 2019 and future trend predictions.

Understanding the global burden of gout in the past and future can provide important references for optimizing prevention and control strategies in healthcare systems. This study aimed to report variations in the global disease burden and risk factors of gout in 204 countries and territories from 1990 to 2019. We conducted a retrospective analysis of gout based on the latest Global Burden of Disease (GBD) 2019 database. We collected data on the prevalence, incidence, and disability-adjusted life years (DALYs) of gout from 1990 to 2019. The data were then stratified by age, sex, and economic development level. Decomposition analysis, frontier analysis, and prediction models were used to analyze the changes and influencing factors influencing each indicator. Globally, there were 53,871,846.4 [95% uncertainty interval (UI): 43,383,204.6-66,342,327.3] prevalent cases, 92,228,86.8 (95% UI: 7419,132.1-11,521,165) incident cases, and 1673,973.4 (95% UI: 1,068,061.1-2,393,469.2) cases of DALYs of gout in 2019, more than double those in 1990. Moreover, the pace of increase in the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized DALY rate (ASDR) accelerated during 1990-2019, with estimated annual percentage changes (EAPC) of 0.94 [95% confidence interval (CI): 0.85-1.03], 0.77 (95% CI: 0.69-0.84), and 0.93 (95% CI: 0.84-1.02), respectively, especially among men. The disease burden of gout has increased in all the other 20 GBD regions in the past 30 years, except Western Sub-Saharan Africa. The highest risk of high body mass index (BMI) and kidney dysfunction was in high-income countries such as North America and East Asia. The global prevalence rate, incidence rate, and DALYs rate of gout in 2030 will reach 599.86, 102.96 per 100,000 population, and 20.26 per 100,000 population, respectively, roughly the same as in 2019. With the development of society, the disease burden of gout will become increasingly severe. It is very important to study the accurate epidemiological data on gout for clinical diagnosis and treatment and health policy.

Awareness of gout disease among adult population in Jazan, Saudi Arabia

Background: Gout is the most prevalent type of inflammatory arthritis, significantly impacting individuals\&amp;apos; quality of life. In the majority of cases, the first metatarsophalangeal joint experiences severe pain, edema, redness, and heat. In recent years, the incidence of gout has considerably increased. This study aimed at assessing the awareness of gout disease among adult population in Jazan, Saudi Arabia. Method: This cross-sectional study was conducted among adults in Jazan, Saudi Arabia, from February to March 2023. Data were collected through an electronic questionnaire, including inquiries about socio-demographic characteristics and awareness of gout disease. SPSS version 27 was used for data analysis, and chi-square tests were employed to assess factors associated with gout awareness. Results: There were 896 participants, with the majority (53.6%) being females. Most participants (48.7%) had a normal body mass index. Only 4% of the participants had gout. We found that 27.1% of participants had poor, 43.9% had moderate, and 29.1% had excellent gout awareness. There was a significant correlation between participants\&amp;apos; awareness scores and their education level, presence of gout disease, family history of gout, and the source of information about gout. Conclusion: Gout stands out as the most common inflammatory arthritis, imposing a significant financial and health burden globally. In the Jazan region, the general population exhibited an inadequate level of awareness about gout. To enhance awareness of this crucial topic and minimize complications, campaigns, media, social media, and conferences are needed to educate Saudis about gout. These initiatives should focus on gout risk factors, symptoms, and genetic predisposition

Chronic tophaceous gout – A case report

Gout is an inflammatory arthritis associated with functional impairment and impact on quality of life. It arises when the tissues are supersaturated with urate leading to the formation of mono sodium urate crystals in and around the joints. This causes an inflammatory cascade resulting in secretion of several proinflammatory cytokines and neutrophil recruitment into the joint.A 60 years old male patient presented with complaints of swelling in the posterior aspect of left elbow since 2 years and pain since 15 days. Examination revealed soft tissue swellings in multiple joints including metatarsophalangeal joint. Renal function tests show increased Uric acid (8.6mg/dl). On Gross examination, we received fibrofatty mass measuring 3.5x1.5x1 cm. Cut-section showed white flakes ? Calcifications. On microscopy, sections studied show fibrocollagenous tissue with several tophi made up of pink eosinophilic material surrounded by foreign body giant cell reaction and lymphocytes. There are several cystic spaces filled with calcareous debris.Hyperuricemia is the key risk factor for gout and is considered prerequisite for mono sodium urate crystal formation. Urate under excretion through kidney is the major mechanism for hyperuricemia. Tophus formation is the cardinal feature of advanced gout.

"Dialogue Between Franklin and the Gout" Reexamined.

Benjamin Franklin, one of the founding fathers of the United States, was not just a politician and a political philosopher but an inventor with a scientific temperament. He was overweight and likely suffered from the consequences of metabolic syndrome including gout. He woke up with a gout attack on October 22, 1780 and wrote the "Dialogue Between Franklin and the Gout." His observations on the risk factors for gout are re-examined in the modern context 243 years later.

Gout in Paleopathology: A Review with Some Etiological Considerations

Gout has been part of human history for thousands of years. Skeletal evidence of the disease among past people in Europe is often associated with high-status individuals whose lifestyles comprised risk factors for gout, including increased sedentism and greater access to rich, high-caloric, food. A growing body of evidence, however, has shown that multiple factors other than lifestyle also contribute to gout development. In 2011, Buckley presented a review of modern and pre-modern gout cases in which she proposed that selective pressures may partly underlie the high prevalence of gout in the population history of the Pacific region. In this paper, we provide an update on Buckley’s 2011 review of gout in human history. We also review early life stress as a potential underlying factor to consider for gout development, particularly among small prehistoric communities where opulent lifestyles traditionally associated with gout were unlikely to have occurred.

Asymptomatic hyperuricemia associated with increased risk of nephrolithiasis: a cross-sectional study

BackgroundExisting evidence shows that there is an independent correlation between nephrolithiasis and gout, and hyperuricemia is the most important risk factor for gout. However, hyperuricemia was often used as an accompanying symptom of gout to explore its association with nephrolithiasis, there were few studies to explore whether hyperuricemia itself or serum uric acid (SUA) is related to the risk of nephrolithiasis. Evidence on the relationship between hyperuricemia and nephrolithiasis is still insufficient.MethodsA total of 22,303 participants aged 30 to 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study in Yunnan Province from May 2018 to September 2019 were included in the study. All participants received standardized face-to-face interviews, medical examinations, and biochemical examinations. Logistic regression was used to estimate the association between hyperuricemia and nephrolithiasis, and a restricted cubic spline (RCS) model was used to explore the dose–response relationship between SUA and the risk of nephrolithiasis.Results14.5% of all participants were diagnosed with hyperuricemia, and 12.1% were diagnosed with nephrolithiasis. After adjusting for all potential confounders, the OR (95%CI) for nephrolithiasis in participants with hyperuricemia compared with participants without hyperuricemia was 1.464 (1.312,1.633), p < 0.001. Restricted cubic spline regression analysis showed that the risk of nephrolithiasis increased with the increase of SUA, and when the level of SUA is higher than 356 μmol/L in males and higher than 265 μmol/L in females, there is a dose–response relationship between the increase of SUA and the risk of nephrolithiasis in both males and females (p for nonlinearity = 0.1668, p for nonlinearity = 0.0667).ConclusionAsymptomatic hyperuricemia is associated with an increased risk of developing nephrolithiasis. Before reaching the diagnostic criteria for hyperuricemia, the risk of nephrolithiasis rises with the increase in SUA. This suggests that controlling SUA levels may be significant for the prevention of nephrolithiasis.

Prediagnostic Glycoprotein Acetyl Levels and Incident and Recurrent Flare Risk Accounting for Serum Urate Levels: A Population-Based, Prospective Study and Mendelian Randomization Analysis.

To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate. We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) for the association with recurrent flares among incident gout cases. Correcting for multiple testing, 88 metabolites were associated with risk of incident gout (N=1,303 cases) before serum urate adjustment, including glutamine and glycine (inversely), and lipids, branched-chain amino acids, and most prominently, glycoprotein acetyls (GlycA; P = 9.17 × 10-32 ). Only GlycA remained associated with incident gout following urate adjustment (HR 1.52 [95% confidence interval (95% CI) 1.22-1.88] between extreme quintiles); the HR increased progressively with fasting duration before sample collection, reaching 4.01 (95% CI 1.36-11.82) for ≥8 hours of fasting. Corresponding HRs per SD change in GlycA levels were 1.10 (95% CI 1.04-1.17) overall and 1.54 (95% CI 1.21-1.96) for ≥8 hours of fasting. GlycA levels were also associated with recurrent gout flares among incident gout cases (RR 1.90 [95% CI 1.27-2.85] between extreme quintiles) with larger associations with fasting. Mendelian randomization corroborated a potential causal role for GlycA on gout risk. This prospective, population-based study implicates GlycA, a stable long-term biomarker reflecting neutrophil overactivity, in incident and recurrent gout flares (central manifestation from neutrophilic synovitis) beyond serum urate.

GLUT9 as a potential drug target for chronic kidney disease: Drug target validation by a Mendelian randomization study.

Although chronic kidney disease (CKD) is recognized as a major public health concern, effective treatment strategies have yet to be developed. Identification and validation of drug targets are key issues in the development of therapeutic agents for CKD. Uric acid (UA), a major risk factor for gout, has also been suggested to be a risk factor for CKD, but the efficacy of existing urate-lowering therapies for CKD is controversial. We focused on five uric acid transporters (ABCG2, SLC17A1, SLC22A11, SLC22A12, SLC2A9) as potential drug targets and evaluated the causal association between serum UA levels and estimated glomerular filtration rate (eGFR) using single-SNP Mendelian Randomization. The results showed a causal association between genetically predicted changes in serum UA levels and eGFR when genetic variants were selected from the SLC2A9 locus. Estimation based on a loss-of-function mutation (rs16890979) showed that the changes in eGFR per unit increase in serum UA level was -0.0082 ml/min/1.73 m2 (95% CI -0.014 to -0.0025, P = 0.0051). These results indicate that SLC2A9 may be a novel drug target for CKD that preserves renal function through its urate-lowering effect.