Risk Factors For Gout Research Articles

Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial.

Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19-60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (SD 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95% CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males.

Obésité, hyperuricémie et goutte

The associations between hyperuricemia and comorbidities, such as hypertension, obesity, and metabolic syndrome (MS), have been shown in many epidemiologic studies. The interactions between serum uric acid (sUA) and other metabolic comorbidities increase the risk of gout. BMI is associated with increased risk of gout according to a dose-dependent effect. The prevalence of MS is remarkably high among individuals with gout and increases substantially with increasing levels of serum uric acid. Several components of the metabolic syndrome have been shown to be independent risk factors for the development of gout. Obesity and hypertriglyceridemia may potentiate a sUA effect for gout development. Gout is associated with an increased risk of developing Diabetes Mellitus: insulin resistance plays a potentially key role in the causal relationship between metabolic syndrome, type 2 diabetes and hyperuricemia. Hypertension was found to be an independent risk factor for gout in several studies. Hyperuricemia also could predict the development of obesity, metabolic syndrome and diabetes, hypertension and cardiovascular diseases. Weight loss has urate-lowering benefits in obese hyperuricaemic or gout patients, and improves comorbidities associated with obesity, as bariatric surgery did. Evidence regarding the therapeutic benefit of dietary modification in patients with gout is low. Lifestyle modification can reduce the risk of recurrent gout, but would also contribute to improve major health in decreasing the risk of cardiovascular disease. The lifestyle and pharmacologic measures that can improve serum urate level and comorbidities together should be preferred.

Association analysis of five SNP variants with gout in the Minnan population in China

There is a very high prevalence of gout in the Minnan population in China. We aimed to explore the genetic characteristics and genetic mechanisms of gout in the Minnan population by studying the association of 5 single nucleotide polymorphisms (SNPs) with gout. A total of 163 gout patients and 187 normal controls from Minnan were enrolled in this case-control study. SNPs (rs1165205, rs3733591, rs6855911, rs2231142, rs333049) were genotyped by allele-specific polymerase chain reaction (PCR) and analyzed with SPSS 16.0. Significant association with gout was found for rs2231142 (P < 0.001), consistent with our prior studies. An association between rs1333049 and gout was also found (P = 0.03) in the Minnan population. No association of SNPs rs6855911, rs3733591, and rs1165205 was found with gout in the Minnan population. Rs1333049 is associated with gout in the Minnan population, although rs2231142 shows an even stronger association with gout. The C allele of rs1333049 and the A allele of rs2231142 might be crucial risk factors for gout.

Effect of a traditional Chinese medicine prescription Quzhuotongbi decoction on hyperuricemia model rats studied by using serum metabolomics based on gas chromatography-mass spectrometry.

Morbidity of hyperuricemia has constantly increased in population in decades, and hyperuricemia has proved to be an important risk factor for gout, cardiovascular diseases and others. Many urate-lowering drugs have unfavorable side effects and drug interactions. Quzhuotongbi decoction (QZTBD) is an empirical traditional Chinese medicine prescription for clinical therapy of hyperuricemia without serious adverse effects. In the study, we investigated the effects of QZTBD on urate and other metabolites in the sera of hyperuricemia model rats. Hyperuricemia model was established by orally administering yeast extract paste, and allopurinol served as a positive control drug. Serum metabolomics was performed by using a gas chromatography-mass spectrometry (GC-MS) method. Student's t-test and the principal component analysis (PCA) were employed to find the metabolic perturbations in hyperuricemia model rats. The levels of urate, lactate, pyruvate and ornithine were significantly increased, and xanthine, glyconic acids (ribonate, galactonate), amino acids (aspartate, proline, glutamine, serine, pyroglutamate, glutamate) and glucose were down-regulated greatly in the model rats. It demonstrated that nucleotide metabolism, amino acid metabolism and glycolytic pathway were disturbed by yeast administration. An orthogonal signal correction-partial least-squares discriminant analysis (OSC-PLS DA) was performed to assess the effects of yeast administering and drug treatment. 11 significantly distinctive metabolites among four groups were defined according to the variable importance for project values (VIP>1) and univariate ANOVA (p value<0.05). As compared to the model rats, the serum uric acid levels were lowered markedly under the treatment of allopurinol or QZTBD. Aspartate and glutamine involved in purine metabolism, were raised to normal level as well. The different influences on xanthine, glutamate pyroglutamate and galactonate suggested there were different mechanisms of two drugs in urate-lowering therapy. Our finding proved that QZTBD can efficiently lower the level of serum uric acid in a different way from allopurinol, which suggested that QZTBD based on the theory of TCM could be an effective therapeutic option for hyperuricemia.

Serum uric acid levels in patients with Familial Mediterranean Fever and healthy controls

Familial Mediterranean Fever (FMF) is one of the best described auto-inflammatory diseases. It has also been suggested recently that gout is an autoinflammatory disease. Monosodium urate crystals are known to induce inflammation by complex cellular mechanisms, mainly involving inflammasome and toll-like receptors which are also involved in the pathogenesis of inflammation in FMF. Uric acid itself has been reported to influence inflammatory responses. Hyperuricemia is defined as serum uric acid levels > 6.8 mg/dl. In this study, it was aimed to investigate whether uric acid, which is a well-known risk factor for gout, is also a contributory risk factor for FMF.

Chronic kidney disease as a risk factor for incident gout among men and women: retrospective cohort study using data from the Framingham Heart Study

ObjectivesHistorically, the nature of association between chronic kidney disease (CKD) and gouty arthritis has been unclear. The goal of the present study was to test the hypothesis that CKD is...

Gout After Living Kidney Donation: A Matched Cohort Study

In the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donor's risk of gout as serum uric acid concentration increases in donors after nephrectomy. Retrospective matched cohort study using large health care databases. We studied living kidney donors who donated in 1992 to 2010 in Ontario, Canada. Matched nondonors were selected from the healthiest segment of the general population. 1,988 donors and 19,880 matched nondonors were followed up for a median of 8.4 (maximum, 20.8) years. Living kidney donor nephrectomy. The primary outcome was time to a diagnosis of gout. The secondary outcome in a subpopulation was receipt of medications typically used to treat gout (allopurinol or colchicine). We assessed the primary outcome with health care diagnostic codes. Donors compared with nondonors were more likely to be given a diagnosis of gout (3.4% vs 2.0%; 3.5 vs 2.1 events/1,000 person-years; HR, 1.6; 95% CI, 1.2-2.1; P<0.001). Similarly, donors compared with nondonors were more likely to receive a prescription for allopurinol or colchicine (3.8% vs 1.3%; OR, 3.2; 95% CI, 1.5-6.7; P=0.002). Results were consistent in multiple additional analyses. The primary outcome was assessed using diagnostic codes in health care databases. Laboratory values for serum uric acid and creatinine in follow-up were not available in our data sources. The findings suggest that donating a kidney modestly increases an individual's absolute long-term incidence of gout. This unique observation should be corroborated in future studies.

Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: a case control study.

IntroductionGout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities. However, a substantial number of non-obese patients (body mass index [BMI] <25 kg/m2) also develop gout in Korea. It was suggested that accumulation of visceral fat rather than subcutaneous fat is associated with metabolic abnormalities and hyperuricemia in patients with gout; therefore, we hypothesized that visceral fat accumulation was increased in non-obese gout patients.MethodsOne hundred and three male patients with primary gout and 204 age-matched healthy controls who attended a health check-up examination were recruited after the review of medical charts. The visceral fat area (VFA) was measured using the bioelectrical impedance analysis (BIA) method, and a VFA >100 cm2 was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequencies of metabolic syndrome and related parameters were also investigated.ResultsBMI, waist circumference, total fat mass, serum triglycerides, and serum glucose levels were significantly greater in patients compared with controls. VFA and the prevalence of VFO was increased in gout patients compared with controls. There were positive correlations between VFA and serum triglyceride levels and serum glucose levels. Multivariate regression analysis revealed that VFO is an independent risk factor for gout (odds ratio 2.488, 95% confidence interval 1.041–4.435). In non-obese subgroup analyses (gout patients, n = 38; healthy controls, n = 150), VFA (98.7 ± 19.3 vs. 91.0 ± 16.7, P = 0.016) and the frequency of VFO (47.4 vs. 27.3%, P = 0.017) remained significantly higher in gout patients. There was no difference in either BMI or total fat mass between patients and controls in the non-obese subgroup. The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104), compared with 13.2% (5/38) in the non-obese subgroup according to modified ATP III criteria.ConclusionVFO, measured using BIA, is observed more frequently in patients with primary gout compared with healthy controls, even in non-obese individuals. Therefore, VFO might more properly represent metabolic derangements in patients with gout than general obesity.

Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population.

In this study, we analyzed single nucleotide polymorphisms (SNP) in urate transporter genes to examine the pathogenesis of gout. We conducted a 1:1-matched case-control study that included 110 patients with acute gout attacks as the patient group and 110 healthy age- and gender-matched subjects as the control group. Clinical parameters were recorded and blood biochemistry tests were conducted for both groups. Multivariate logistic regression analysis was used to analyze the data. Hyperuricemia, hypercholesterolemia, and hypertriglyceridemia were found to be the main risk factors for the onset of gout, with relative risks of 29.2 (P < 0.001), 25.5 (P = 0.003), and 11.2 (P < 0.001). For all detected SNP, rs2231142, located in ABCG2, showed the largest frequency differences for the G/G, G/T, and T/T genotypes between groups: the distribution of these genotypes in the case group was 22, 49, and 26 individuals, respectively, and was 54, 38, and 9 individuals, respectively, in the control group. There was a statistically significant difference between the 2 groups (P < 0.001) and the odds ratio was 7.091 (95% confidence interval = 2.867-17.541). Other SNPs (rs1165196, rs1165205, rs1183201, rs17300741, rs2078267, rs2242206, rs3733591, and rs9358856) showed no significant difference between the groups (P > 0.05). The risk factors of gout were hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and the T/T genotype of the rs2231142 locus in the ABCG2 gene; expression of the G/G genotype may be a protective factor against gout development.

Rapid screening and detection of XOD inhibitors from S. tamariscina by ultrafiltration LC-PDA-ESI-MS combined with HPCCC.

Xanthine oxidase (XOD) catalyzes the metabolism of hypoxanthine and xanthine to uric acid, the overproduction of which could cause hyperuricemia, a risk factor for gout. Inhibition of XOD is a major treatment for gout, and biflavonoids have been found to act as XOD-inhibitory compounds. In this study, ultrafiltration liquid chromatography with photodiode-array detection coupled to electrospray-ionization tandem mass spectrometry (UF-LC-PDA-ESI-MS) was used to screen and identify XOD inhibitors from S. tamariscina. High-performance counter-current chromatography (HPCCC) was used to separate and isolate the active constituents of these XOD inhibitors. Furthermore, ultrahigh-performance liquid chromatography (UPLC) and triple-quadrupole mass spectrometry (TQ-MS) was used to determine the XOD-inhibitory activity of the obtained XOD inhibitors, and enzyme kinetics was performed with Lineweaver-Burk (LB) plots using xanthine as the substrate. As a result, two compounds in S. tamariscina were screened as XOD inhibitors: 65.31mg amentoflavone and 0.76mg robustaflavone were isolated from approximately 2.5g S. tamariscina by use of HPCCC. The purities of the two compounds obtained were over 98% and 95%, respectively, as determined by high-performance liquid chromatography (HPLC). Lineweaver-Burk plot analysis indicated that amentoflavone and robustaflavone were non-competitive inhibitors of XOD, and the IC 50 values of amentoflavone and robustaflavone for XOD inhibition were 16.26μgmL(-1) (30.22μmolL(-1)) and 11.98μgmL(-1) (22.27μmolL(-1)), respectively. The IC 50 value of allopurinol, used as the standard, was 7.49μgmL(-1) (46.23μmolL(-1)). The results reveal that the method for systematic screening, identification, and isolation of bioactive components in S. tamariscina and for detecting their inhibitory activity using ultrafiltration LC-ESI-MS, HPCCC, and UPLC-TQ-MS is feasible and efficient, and could be expected to extend to screening and separation of other enzyme inhibitors.

OP0136 Sex Differences in Gout Characteristics: Tailoring Care for Women and Men

ObjectivesUsing a national registry of gout patients cared for by rheumatologists, we sought to characterize the differences between women and men with gout, in terms of predisposing factors, comorbid conditions,...

Gout in African Americans

PurposeAfrican Americans have a substantially higher prevalence of risk factors for gout than Caucasians. The aim of the present study was to compare the risk for incident gout among African Americans and Caucasians. MethodsIncidence rates of physician-diagnosed gout among 11,559 Caucasian men and 931 African American men aged 35 to 57 years and at high cardiovascular risk, observed for 7 years as a part of the Multiple Risk Factor Intervention Trial, were analyzed. Cox regression models were used to account for potential confounding by age, body mass index, diuretic use, hypertension and diabetes status, aspirin and alcohol consumption, and kidney disease. ResultsAt baseline, after accounting for risk factors, African Americans had a 14% lower prevalence of hyperuricemia than Caucasians. Incidence of gout increased with increasing prevalence of risk factors in both Caucasians and African Americans. Ethnic disparities in incidence rates were most apparent among those without other risk factors for gout. In separate Cox regression models, after accounting for risk factors, African American ethnicity was associated with a hazard ratio of 0.78 (95% confidence interval [CI], 0.66-0.93) for physician-diagnosed gout and 0.88 (95% CI, 0.85-0.90) for incident hyperuricemia. Significant interactions were observed; the association was the strongest (hazard ratio 0.47; 0.37-0.60). These associations were unaffected by addition of serum urate as a covariate or by using alternate case definitions for gout. ConclusionsAfter accounting for the higher prevalence of risk factors, African American ethnicity is associated with a significantly lower risk for gout and hyperuricemia compared with Caucasian ethnicity.

275. Crystal Clear? A Case-Control Study of the Prevalence of and Risk Factors for Gout in the HIV-Infected Population

275. Crystal Clear? A Case-Control Study of the Prevalence of and Risk Factors for Gout in the HIV-Infected Population

Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study

ObjectivesTo assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using...

Definition of hyperuricemia and gouty conditions

To define gout conditions and hyperuricemia. Gout is defined as an arthritic condition resulting from the deposition of monosodium urate (MSU) crystals in and/or around joints, following long-standing hyperuricemia. Several recent ultrasound studies disclosed MSU deposits in a large proportion of asymptomatic hyperuricemic patients. A gout condition defined by asymptomatic MSU deposits can therefore be individualized. Such asymptomatic deposits appear to precede the occurrence of flares, which seem to be triggered by mobilization of preformed crystals. Hyperuricemia appears to be the main, if not the only, risk factor for gout. Recent studies also support the view that hyperuricemia is an independent risk factor for renal and cardiovascular diseases. The level at which uricemia becomes abnormal is still disputed. This lack of consensus precludes comparison of studies using different definitions and impairs the understanding of gout by doctors and patients. We propose to define hyperuricemia as greater than 6 mg/dl, as the life-long risk of gout seems to start at this level. This definition is identical to the minimum uricemia target of urate-lowering drugs (ULDs). Asymptomatic MSU crystals deposits can now be identified and precede the onset of gout flares. Defining hyperuricemia as greater than 6 mg/dl would have the advantage to give the same value for normal and ULD-targeted uricemia, which would facilitate patients' adherence to this target.

The Crystallization of Monosodium Urate

Gout is a common crystal-induced arthritis, in which monosodium urate (MSU) crystals precipitate within joints and soft tissues and elicit an inflammatory response. The causes of elevated serum urate and the inflammatory pathways activated by MSU crystals have been well studied, but less is known about the processes leading to crystal formation and growth. Uric acid, the final product of purine metabolism, is a weak acid that circulates as the deprotonated urate anion under physiologic conditions, and combines with sodium ions to form MSU. MSU crystals are known to have a triclinic structure, in which stacked sheets of purine rings form the needle-shaped crystals that are observed microscopically. Exposed, charged crystal surfaces are thought to allow for interaction with phospholipid membranes and serum factors, playing a role in the crystal-mediated inflammatory response. While hyperuricemia is a clear risk factor for gout, local factors have been hypothesized to play a role in crystal formation, such as temperature, pH, mechanical stress, cartilage components, and other synovial and serum factors. Interestingly, several studies suggest that MSU crystals may drive the generation of crystal-specific antibodies that facilitate future MSU crystallization. Here, we review MSU crystal biology, including a discussion of crystal structure, effector function, and factors thought to play a role in crystal formation. We also briefly compare MSU biology to that of uric acid stones causing nephrolithasis, and consider the potential treatment implications of MSU crystal biology.

Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians

Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal and cardiovascular diseases, is caused by either increased production or decreased excretion of uric acid or a mix of both. The solute carrier protein 2 family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux across the renal proximal tubule. Genome-wide association studies have consistently shown the association of single-nucleotide polymorphisms in this gene with SUA in majority populations. American Indian participants of the Strong Heart Family Study, belonging to multigenerational families, have high prevalence of hyperuricemia. We conducted measured genotype analyses, based on variance components decomposition method and accounting for family relationships, to assess whether the association between SUA and SLC2A9 gene polymorphisms generalized to American Indians (n=3604) of this study. Seven polymorphisms were selected for genotyping based on their association with SUA levels in other populations. A strong association was found between SLC2A9 gene polymorphisms and SUA in all centers combined (P-values: 1.3 × 10(-31)-5.1 × 10(-23)) and also when stratified by recruitment center; P-values: 1.2 × 10(-14)-1.0 × 10(-5). These polymorphisms were also associated with the estimated glomerular filtration rate and serum creatinine but not albumin-creatinine ratio. In summary, the association of polymorphisms in the uric acid transporter gene with SUA levels extends to a new population of American Indians.

Contemporary epidemiology of gout and hyperuricemia in community elderly in Beijing

To evaluate the prevalence and risk factors of gout and hyperuricemia in an elderly community cohort in Beijing. A total of 10 039 individuals aged 50 years or older participated in the study, based on the Beijing Longitudinal Study on Aging II (BLSA II) Cohort in 2009. All participants were asked for a Gout Assessment Questionnaire under the guidelines of the American College of Rheumatology. The prevalence of gout and hyperuricemia were evaluated. The potential risk factors for gout and hyperuricemia were analyzed by logistic regression. In our BLSA II cohort, the prevalence of gout and hyperuricemia were 2.8% and 18.1%, respectively. The prevalence of gout in the Han population was significantly lower than that in Hui population (2.6% vs. 5.8%). The traditional risk factors (age and body mass index [BMI] and metabolic syndrome [ms]) were significantly associated with the risk of gout and hyperuricemia (age: OR 1.2, 95%CI 1.1-1.5 for gout; OR 1.3, 95%CI 1.1-1.4 for hyperuricemia, respectively; BMI: OR 1.6, 95%CI 1.3-2.0; OR 1.5, 95%CI 1.3-1.8; ms: OR 2.6, 95%CI 2.0-3.3; OR 2.0, 95%CI 1.7-2.2). Family history was strongly associated with an increased risk of gout (OR 6.5, 95%CI 3.9-10.8). Our study showed that the prevalence of both gout and hyperuricemia in Beijing remains substantial. The prevalence in the Hui population was higher than other ethnic groups. The traditional risk factors were strong risk factors for gout and hyperuricemia in China.

Occurrence of gout in rheumatoid arthritis: it does happen! A population-based study

It has been a popular belief that gout does not typically occur in patients with rheumatoid arthritis (RA). Our aim was to assess the occurrence, prevalence, clinical presentation and possible risk factors for gout in patients with RA. We retrospectively reviewed a population-based incidence cohort of patients who fulfilled 1987 ACR criteria for RA between 1980 and 2007. The cumulative prevalence of gout in RA adjusted for the competing risk of death was estimated. Among the 813 patients with RA, six were diagnosed with gout prior to RA incidence and 22 patients developed gout during a total of 9771 person-years of follow-up. Nine out of 22 patients had crystal-proven gout. The 25-year cumulative prevalence of gout diagnosed by clinical criteria in patients with RA was 5.3%. Gout does occur in patients with rheumatoid arthritis, however, at a lower rate than in the general population.

SAT0457 Consumption of green tea and alcohol, and serum urate levels: The singapore chinese health study

BackgroundHyperuricaemia is a risk factor for gout, diabetes, hypertension, kidney and cardiovascular diseases as well as mortality. Beverages form an important part of diet which may affect serum urate (SUA)...