Influence Serum Uric Acid Levels Research Articles

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort

BackgroundMost of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia.MethodCross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample.ResultsThe reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3–7.0] for men versus 4.5 [3.9–5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8–33.0%) in men and 4.8% (95% CI 4.3–5.3%) in women.ConclusionSUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women.

This study examines associations between the ESR1 (XbaI, PvuII) and the MLXIPL (rs3812316) gene polymorphisms, and uric acid (UA) levels in Slovak midlife women, subdivided according to their menopause status. We assessed a total of 362 women from 38 to 65 years of age. Women were recruited from different localities in the western and middle parts of Slovakia. Participants were interviewed during their medical examination at local health centers. They were investigated with respect to a variety of aspects such as medical, anthropometrical, and lifestyle. Participants provided a blood sample for biochemical analyses and DNA genotyping. The MLXIPL gene (rs3812316 SNP variant) and ESR1 gene (PvuII and XbaI) genotypes were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using general linear models and multiple linear regression analyses to adjust for risk factors elevating the UA level such as fat mass (FM), triglycerides (TGs) and creatinine. A positive association between MLXIPL and UA level was observed in the total sample of women after control for confounding covariates, including FM, TGs, and creatinine (P = 0.027). Women with the CC genotype had higher UA levels than the G-allele carriers (261.5 μmol/L ± 68.3 vs 241.1 μmol/L ± 55.1 P = 0.013). A statistically significant association was noticed between postmenopause status and the ESR1 XbaI genotype and their effect on UA (P = 0.028). The Bonferroni pairwise comparison determined that the G-allele carriers in the postmenopausal period had higher estimated UA marginal mean (269.7 μmol/L) than the AA-allele postmenopausal women (236.5 μmol/L) (P = 0.012). The estimated UA marginal mean showed a significant increasing trend according to the MS in G allele carriers (248.5 μmol/L in pre/peri-menopausal vs 269.7 μmol/L in postmenopausal, P = 0.009). In contrast, a decreasing trend was observed in AA carriers (250.6 μmol/L in pre/perimenopausal women vs 236.5 μmol/L in postmenopausal). However, this trend was not statistically significant (P = 0.288). This cross-sectional study suggests that MLXIPL (rs3812316) polymorphism is associated with higher serum UA levels and that the ESR1 (XbaI) polymorphism is associated with UA levels only in the postmenopausal cohort.

Reference interval and upper decission limit for serum uric acid – an evidence-based approach on Romanian population using an a posteriori method

Abstract Introduction. There is accumulating evidence that high normal serum uric acid (SUA) levels of 6-7 mg/dL are associated with cardiovascular morbidity and metabolic syndrome (MetS), hence the need to redefine its upper limit of normal (ULN). We aimed to derive ULN based on statistics and evidence in a representative sample of the population and to observe its relation to MetS components. Methods. All SUA measurements form a university rheumatology hospital were extracted between January 5th 2010 and March 21st 2018. SUA levels were measured by a single biochemist a unique type of commercially available kit. Follow-up measurements, patients with diagnoses influencing SUA levels and outlying measurements were excluded. ULNs were studied using least square analysis. Results. Of the 22503 SUA measurements in the database, only 3318 came from normal individuals: 33.3% men (n=1105), 66.7% women (n = 2213). Least square analysis revealed the following SUA reference intervals (RI): 3.43-6.19 mg/dL for the combined sample; 4.44-7.01 mg/dL for men, 3.28-5.56 mg/dL for women. The values corresponding to the 66th percentile of each group presented lower ULNs: 5.36 mg/dL for all, 6.10 mg/dL for men, 4.90 mg/dL for women. The prevalence of hyperuricemia increased from 13.8% (manufacturer’s gender-specific ULN) to 19.9% (derived ULN). Mean SUA levels significantly increased with the number of MetS components. Conclusion. We recommend that hyperuricemia should be defined using a statistical approach of ULN selection corresponding to the genderand population-specific 66th percentile of data range.

Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine

Ethnopharmacological relevanceCordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of “protecting liver and enhancing kidney functions”, influencing serum uric acid levels. Aim of studyThe aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice. Materials and methodsA water extract (WECM) was prepared by decocting C. militaris directly at 80 °C in water bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5mg/kg) was served as a positive control. ResultsWECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306μmol/L) to 189, 184 and 162μmol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184μmol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between −200 and −400kcal/mol. ConclusionsThese findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work.

Nonpharmacological Management of Gout and Hyperuricemia: Hints for Better Lifestyle.

We reviewed lifestyle factors that influence serum uric acid levels and risk of gout flare, and how to improve their deleterious effects. Since obesity increases uric acid and weight gain increases gout risk, weight reduction by daily exercise and limiting intake of excess calories is recommended. However, strenuous exercise, which causes adenine nucleotide degradation; starvation, which decreases uric acid excretion; and dehydration may raise the level of uric acid in serum and trigger gout. Increased intake of purine-rich foods, such as meat and seafood, raise the level of uric acid in serum and is associated with increased risk of gout, whereas dairy products, especially low-fat types, are associated with a lower risk of gout. Also, heavy alcohol drinking raises the uric acid level and increases the risk of gout through adenine nucleotide degradation and lactate production. Sweet fruits and soft drinks containing fructose should be moderated, since fructose may raise uric acid and increase gout risk through uric acid production and/or decreased excretion. On the other hand, the Mediterranean diet is recommended for gout patients, since it may also help prevent hyperuricemia. Furthermore, coffee and vitamin C supplementation could be considered as preventive measures, as those can lower serum uric acid levels as well as the risk of gout.

Relation of serum uric acid to cardiovascular disease.

This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied.

Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study

Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in children. Prospective observational cohort study. Children and adolescents (n=678 cross-sectional; n=627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years enrolled at 52 North American sites of the CKiD (CKD in Children) Study. Serum uric acid level (<5.5, 5.5-7.5, and >7.5mg/dL). Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy. Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0, and≥2.0mg/mg), age- and sex-specific body mass index > 95th percentile, use of diuretics, and serum uric acid level. Older age, male sex, lower GFR, and body mass index > 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels < 5.5, 5.5 to 7.5, or >7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels< 5.5mg/dL, those with uric acid levels of 5.5 to 7.5 or >7.5mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point. The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels and CKD progression. Hyperuricemia is a previously undescribed independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression.

Functional Polymorphisms of the ABCG2 Gene Are Associated with Gout Disease in the Chinese Han Male Population

BackgroundGout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population.MethodsPeripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K.ResultsFor Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77–2.74, p = 8.99 × 10−13). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49–5.68, p = 1.57 × 10−3). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43–0.71, p = 2.55 × 10−6). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR = 2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.ConclusionThe ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.

Uric Acid and Coronary Collateral Circulation

Coronary collateral (CC) artery development is usually attributed to ischemia, but these anastomotic channels are also present in individuals who do not have coronary artery disease (CAD). The CCs are present in one-fourth of the patients with normal coronary arteries or nonobstructive CAD. Currently, there is no noninvasive method for evaluating CC circulation in humans. The most widely used strategy is visual assessment of collateral arteries as described by Rentrop et al. This method involves balloon occlusion of the contralateral coronary artery, which is rarely performed. In clinical practice, this method is applied without occluding the contralateral vessels. As a result, underestimation of collateralization is inevitable. Other limitations of this visual method include observer variability, influence by the blood pressure, and the force of contrast injection as well as the duration of filming. The most accurate assessment could be obtained by measuring the pressure-derived collateral flow index. Several clinical and angiographic variables including the degree of coronary stenosis, proximal lesion location, longer duration of symptoms, and occlusion as well as resting bradycardia have been reported as variables that correlated with the degree of collateralization. Also, in patients without CAD, the baseline heart rate has been described as the main predictor of collateralization. The most important trigger for collateral growth is tangential (radial) fluid shear stress at the endothelial level with the recruitment of bone marrow-derived mononuclear cells. It is a remodeling process of preexisting small collateral arterioles rather than the growth of new capillary vessels, which is induced by ischemia. Collateral growth is induced by fluid shear stress in preformed collateral vessels caused by a pressure gradient between the area proximal to a coronary stenosis and the low-pressure poststenotic area. The CCs play a role in preserving myocardial function, limiting infarct size, and increasing survival. However, a meta-analysis showed that a well-developed collateral circulation was a risk factor for restenosis after coronary revascularization. In humans, uric acid (UA) is generated from purine catabolism with the conversion of hypoxanthine to xanthine and of xanthine to UA by the enzyme xanthine oxidoreductase. It is further oxidized to allantoin in most species except humans and some higher primates who lack uricase. Therefore, serum UA (SUA) levels in humans are appreciably higher than in other mammals. Because of this difference in urate metabolism, the results of animal studies can be difficult to interpret. Also, different methods of measuring collateral flow may be applied in animal studies. Many patients with CAD use at least 1 drug that can influence SUA levels (eg, aspirin, statins, fibrates, and some antihypertensive agents). The SUA levels are higher in men than in women at all ages due to gender steroids. Sumino et al showed that hormone replacement therapy in postmenopausal women was associated with a significant reduction in SUA level. Also, dietary, environmental, and genetic factors are important determinants of SUA levels. It is important to note that UA is a potent antioxidant, but it can also be a prooxidant if the level is >6 mg/dL in women and 6.5 to 7.0 mg/dL in men. Therefore, elevated SUA level might be an indicator of increased burden of oxidant attack. Besides its dual oxidant effect, if UA is a harmful product, why do our kidneys recover 90% of filtered UA instead of eliminating it? Despite the antioxidant properties of UA, several studies have indicated that high SUA levels are associated with several disorders, including CAD, peripheral arterial disease, heart failure, metabolic syndrome, hypertension, and stroke. These associations have been mainly attributed to upregulation of renin release and the subsequent cascade-related reduction in endothelial function. However, instead of proven causal associations, possible explanations with small study groups could be reverse causality. For example, preclinical atherosclerosis could lead to higher levels of SUA. In contrast, experts from the Framingham Heart Study group have reported no association between the SUA and the cardiovascular disease. In a recently published study, Palmer et al investigated the association of plasma UA with CAD and hypertension using Mendelian randomization. They found no evidence of a causal effect of UA or hyperuricemia on the risk of CAD and hypertension. Recently, some studies have demonstrated an association between SUA and CC development in patients with CAD and

Uric Acid and Diabetes: Is there a Link?

Elevated serum uric acid (SUA) levels (i.e. hyperuricaemia) have been associated with metabolic syndrome (MetS) and cardiovascular disease (CVD) morbidity and mortality. Elevated SUA levels predict the onset of type 2 diabetes (T2DM). SUA levels are increased during the early stages of impaired glucose metabolism. Furthermore, in diabetic patients, hyperuricaemia has been linked to both micro- and macrovascular complications. The present review considers: (1) SUA levels in patients with MetS, type 1 diabetes and T2DM; (2) the mechanisms that influence SUA levels in these patients; (3) the potential links between SUA and diabetic complications. The effect on SUA levels of drugs commonly prescribed for T2DM and the risk of uric acid nephrolithiasis in patients with MetS or DM are also briefly discussed.

Novelties in gout

Chronic asymptomatic hyperuratemia (HUA), gout paroxysm in patients with chronic hyperuratemia (HU) and normouricemic attacks of gouty arthritis are well known, but poorly understood. A review of the current literature with attempt of its explanation is presented. The natural course of gout is associated with joint structure changes that may be evaluated by different imaging techniques; comparative advantages and shortcomings of each technique are presented. For almost over 50 years the market has not offered new drugs for the control of HU and gout, while management of such patients was a rather neglected field. Over the last five years an unpredictable number of prospective clinical studies have been conducted involving the investigation of the efficacy and safety of new drugs to control HU (febuxostat, pegloticase). The return of pharmaceutical industry into the world of gout has considerably changed the picture. New recommendations have been presented on appropriate colchicine dose regime for acute gouty flares. Emerging therapies, including pegloticase, uricosuric agent RDEA596 and the interleukin-1 inhibitors have shown promises in early and late phase clinical trials. Each of them deserves to be considered for implementation and feasibility in clinical practice as well as outcome measures for clinical trials. Another purpose of this review was to summarize new knowledge on approved drugs to treat hyperuricemia, or the clinical manifestations of gout. Results of several clinical trials provide new data on the efficacy and safety of the approved urate lowering drugs (allopurinol and febuxostat). Lifestyle and dietary recommendations for gout patients should take into consideration overall health benefits and risks, since gout is often associated with metabolic syndrome and an increased future risk of cardiovascular disease and mortality. This review also summarizes the recent data about lifestyle factors that influence serum uric acid levels and the gout risk, and attempts to provide holistic recommendations, considering both their impact on gout as well as on other health implications.

Significant association of serum uric acid levels with SLC2A9 rs11722228 among a Japanese population

Genome-wide association studies identified that SLC2A9 ( GLUT9) gene polymorphisms were associated with serum uric acid (SUA) levels. Among the Japanese, a C/T polymorphism in intron 8 (rs11722228) was reported to be highly significant, though the function and strength of association were unknown. This study aimed to confirm the association, estimating the means of SUA according to the genotype, as well as OR of the genotype. Subjects were 5024 health checkup examinees (3413 males and 1611 females) aged 35 to 69 years with creatinine < 2.0 mg/dL. Since SLC22A12 258X allele and ABCG2 126X allele are known to influence SUA levels strongly, the subjects with SLC22A12 258WW and ABCG2 126QQ (3082 males and 1453 females, in total 4535 subjects) were selected. The genotype frequency of SLC2A9 rs11722228 was 2184 for CC, 1947 for CT, and 404 for TT, being in Hardy–Weinberg equilibrium (p = 0.312). Mean SUA was 6.10 mg/dL for CC, 6.25 mg/dL for CT, and 6.45 mg/dL for TT among males (p = 1.5E-6), and 4.34 mg/dL, 4.59 mg/dL, and 4.87 mg/dL among females (p = 4.6E-11), respectively. Males with SUA less than 5.0 mg/dL were 14.7% for CC, 10.6% for CT, and 7.8% for TT (p = 2.3E-4), and females with SUA less than 4.0 mg/dL were 34.1%, 25.5%, and 15.4% (p = 3.7E-6), respectively. This study was the first report to estimate the impact of SLC2A9 rs11722228 on SUA levels. Since the allele frequency of rs11722228 is similar among different ethnic groups, the impact remains to be examined in other ethnic groups.

Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease

BackgroundRecently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD.Methods and FindingsA total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p = 5.6*10−7, p = 1.1*10−7, and p = 1.3*10−3, respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls.ConclusionSNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.

New insights into the epidemiology of gout

Gout is a true crystal deposition disease caused by formation of monosodium urate crystals in joints and other tissues. It is a common inflammatory arthritis that has increased in prevalence in recent decades. Gout normally results from the interaction of genetic, constitutional and environmental risk factors. It is more common in men and strongly age related. A major determinant is the degree of elevation of uric acid levels above the saturation point for urate crystal formation, principally caused by inefficient renal urate excretion. Local joint tissue factors may influence the topography and extent of crystal deposition. Recent studies have provided information on dietary risk factors for gout: higher intakes of red meat, fructose and beer are independently associated with increased risk, whereas higher intakes of coffee, low-fat dairy products and vitamin C are associated with lower risk. Several renal urate transporters have been identified including URAT1 and SLC2A9 (GLUT9) and polymorphisms in these genes are associated with an increased risk of hyperuricaemia and gout. Many drugs influence serum uric acid levels through an effect on renal urate transport. Comorbidities, including the metabolic syndrome and impaired renal function are common in gout patients. The usual initial presentation of gout is with rapidly developing acute inflammatory monoarthritis, typically affecting the first MTP joint. If left untreated it may progress with recurrent acute attacks and eventual development of chronic symptoms and joint damage. New knowledge of the modifiable risk factors for gout can be integrated into the management strategy to optimize long-term patient outcomes.

The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts

High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10−16), along with eight others (p = 7.75 × 10−16 to 6.05 × 10−11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.

The GLUT9 Gene is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts

High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10−16), along with eight others (p = 7.75 × 10−16 to 6.05 × 10−11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.

Serum uric acid in normal and hypertensive Australian subjects.

Summary: Hyperuricaemia, defined in relation to serum uric acid (SUA) levels in normal Australian subjects, was found in 48% of 149 hypertensive patients attending the Cardio-Vascular Clinic, Sydney Hospital. Among untreated patients the prevalence was 31%. SUA levels were highest in subjects with renal hypertension and chronic renal failure. Treatment with adrenergic blocking drugs was associated with higher levels of SUA. A correlation between hypertension, hyperuricaemia and hypercholesterolaemia was investigated. Factors influencing SUA levels were analysed and the findings subjected to statistical analysis. SUA levels in normal subjects are higher in the Australian population than in reported overseas series.