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.

Serum uric acid is associated with chronic kidney disease in elderly Chinese patients with diabetes.

BACKGROUND: The relationship between hyperuricemia and chronic kidney disease (CKD) has been investigated extensively. However, studies on elderly individuals are still limited. Moreover, there is no consensus on whether hyperuricemia or elevated serum uric acid (SUA) within the normal range is correlated with the new onset of CKD and whether there are differences between males and females. METHODS: We included 39039 elderly diabetic patients without CKD at baseline from a community-based cohort in Wuhan, China. The outcome event was the new onset of CKD (defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Multivariate Cox models were used to assess the adjusted hazard ratio (HR). RESULTS: During the 2-year follow-up period, 3162 (8.10%) patients with diabetes developed new-onset CKD. The optimal cutoff value of SUA for incident CKD was 347.4 µmol/L. The adjusted HRs of hyperuricemia for new-onset CKD were 1.925 (1.724-2.150) and 1.676 (1.520-1.848) for males and females, respectively. The risk of developing CKD increased across the Q4 group up to 2.242 times for their counterparts in the lowest SUA quartile, independent of age, sex, diabetes duration, obesity, hypertension, systolic blood pressure, diastolic blood pressure, smoking, drinking, dyslipidemia, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting plasma glucose. CONCLUSIONS: Hyperuricemia is an independent predictor of incident CKD. Elevated SUA was linearly correlated with CKD in elderly patients with diabetes, showing a relatively higher intensity among males compared with that among females. The optimal cutoff value of SUA for the risk of new-onset CKD in elderly patients with diabetes was 347.4 µmol/L.

Is hyperuricemia an independent prognostic factor for IgA nephropathy: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND: Hyperuricemia has been reported to be correlated with IgA nephropathy (IgAN). However, whether hyperuricemia or elevated serum uric acid (SUA) is an independent prognostic factor of IgAN remains unknown. Therefore, this systematic review and meta-analysis evaluated the prognostic value of hyperuricemia and elevated SUA in IgAN. METHODS: Databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Open Gray were reviewed systematically. The kidney failure events of IgAN were defined as a doubling of serum creatinine, halving of eGFR, end-stage renal disease (ESRD), or death. The risk ratio (RR) between hyperuricemia and IgAN-caused kidney failure was evaluated before and after adjustment for relevant covariates. The RR between elevated SUA and IgAN-caused kidney failure was evaluated after adjustment for relevant covariates. RESULTS: A total of 11 548 patients from 14 studies were included in this meta-analysis. Hyperuricemia was found to be an independent prognostic factor of IgAN (unadjusted RR = 2.79, 95% CI = 1.93-4.03, p for heterogeneity <0.00001, I2 = 91%; adjusted RR = 2.12, 95% CI = 1.64-2.73, p for heterogeneity = 0.86, I2 = 0%). Subgroup and sensitivity analyses confirmed the stability of these results. Similarly, elevated SUA was positively correlated with kidney failure events of IgAN (adjusted RR = 1.25, 95% CI = 1.19-1.31, p for heterogeneity = 0.6, I2 = 0%). CONCLUSION: Our meta-analysis showed that hyperuricemia and elevated SUA were both independently associated with an increased incidence of kidney failure events in IgAN patients.

High prevalence and low awareness of hyperuricemia in hypertensive patients among adults aged 50-79 years in Southwest China.

INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.

Febuxostat combined with hydration for the prevention of contrast-induced nephropathy in hyperuricemia patients undergoing percutaneous coronary intervention: A CONSORT-compliant randomized controlled trial.

BACKGROUND: To assess the efficacy of febuxostat combined with hydration on contrast-induced nephropathy (CIN) in coronary heart disease patients with hyperuricemia undergoing percutaneous coronary intervention (PCI). METHODS: Patients with hyperuricemia who underwent PCI were randomly assigned to 2 groups. The control group was given hydration only, and the febuxostat group received febuxostat 40 mg daily before administration of contrast agent and hydration. The primary endpoint of the study was the incidence of CIN, defined as an increase in baseline serum creatinine concentration by 25% at 2 days after contrast media administration, and variations in the serum levels of creatinine, neutrophil gelatinase-associated lipocalin, uric acid, and estimated glomerular filtration rate were compared. RESULTS: A total of 202 patients with hyperuricemia were randomly assigned to either the febuxostat group (n = 100) or the control group (n = 102). The baseline characteristics of the 2 groups were similar. The incidence of CIN was 6.0% (6/100) in the febuxostat group and 14.71% (15/102) in the control group.The levels of neutrophil gelatinase-associated lipocalin at 6-hour and serum creatinine and uric acid at 48-hour in the febuxostat combined hydration group were lower than those in the control group after surgery, and the level of estimated glomerular filtration rate was higher than that in the control group (all P < .05). Multivariate logistic regression analysis revealed that febuxostat was an independent predictor of CIN. CONCLUSION: Our study demonstrated that prophylactic treatment with febuxostat combined with hydration can reduce the incidence of CIN in patients with coronary heart disease and hyperuricemia after PCI.

Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort.

Objective: Hyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers. Methods: A Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis. Results: An inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; ß=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels. Conclusions: Serum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.

HbA1c combined with glycated albumin or 1,5-anhydroglucitol improves the efficiency of diabetes screening in a Chinese population.

AIMS: This study aimed to evaluate the ability of HbA1c combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China. METHODS: The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA1c , GA, 1,5-AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA1c , GA and 1,5-AG according to the Youden index. RESULTS: (1) The optimal thresholds of HbA1c , GA and 1,5-AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 µg/ml, respectively. (2) The sensitivities of HbA1c combined with GA and 1,5-AG were both 85%, higher than that of HbA1c (70%, p < 0.001). CONCLUSIONS: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA1c combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricaemia.

Hyperuricemia and the Risk of Heart Failure: Pathophysiology and Therapeutic Implications.

The association between hyperuricemia and cardiovascular disease (CVD) has been reported and studied in the past two decades. Xanthine oxidase (XO) induced uric acid (UA) serves as a risk factor and has the independent prognostic and functional impact of heart failure (HF), but whether it plays a positive role in the pathogenesis of HF has remained unclear. Growing evidence suggest the up-regulated XO avtivity and increased production of free oxygen radical (ROS) correspondingly are the core pathogenesis of HF with hyperuricemia, which results in a whole cluster of pathophysiologic cardiovascular effects such as oxidative stress, endothelial dysfunction, vascular inflammation, left ventricular (LV) dysfunction as well as insulin resistance (IR). The use of XO inhibition represents a promising therapeutic choice in patients with HF due to its dual effect of lowering serum UA levels as well as reducing ROS production. This review will discuss the pathophysiologic mechanisms of hyperuricemia with HF, the targeted therapeutic interventions of UA lowering therapies (ULT) with XO inhibition and mechanism underlying beneficial effects of ULT. In addition, the review also summarizes current evidence on the role of ULT in HF and compares CV risk between allopurinol and febuxostat for practical and clinical purposes. Guidelines and implementation of CV risk management in daily practice will be discussed as well.

Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction.

BACKGROUND: Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. METHODS: This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. RESULTS: Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 µmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 µmol/L) to the lowest tertile (< 341.7 µmol/L) of baseline SUA. CONCLUSIONS: Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.

U-Shaped Association Between Serum Uric Acid and Short-Term Mortality in Patients With Infective Endocarditis.

Background: Increased uric acid (UA) levels have been reported to be associated with poor clinical outcomes in several conditions. However, the prognostic value of UA in patients with infective endocarditis (IE) is yet unknown. Methods: A total of 1,117 patients with IE were included and divided into two groups according to the current definition of hyperuricemia (UA>420 µmol/L in men and >360 µmol/L in women): hyperuricemia group (n=336) and normouricemia group (n=781). The association between the UA level and short-term outcomes were examined. Results: The in-hospital mortality was 6.2% (69/1117). Patients with hyperuricemia carried a higher risk of in-hospital death (9.8% vs. 4.6%, p=0.001). Hyperuricemia was not an independent risk factor for in-hospital death (adjusted odds ratio [aOR]=1.92, 95% confidence interval [CI]: 0.92-4.02, p=0.084). A U-shaped relationship was found between the UA level and in-hospital death (p<0.001). The in-hospital mortality was lower in patients with UA in the range 250-400 µmol/L. The aOR of in-hospital death in patients with UA>400 and <250 µmol/L was 3.48 (95% CI: 1.38-8.80, p=0.008) and 3.28 (95%CI: 1.27-8.51, p=0.015), respectively. Furthermore, UA>400 µmol/L (adjusted hazard ratio [aHR]=3.54, 95%CI: 1.77-7.07, p<0.001) and <250 µmol/L (aHR=2.23, 95%CI: 1.03-4.80, p=0.041) were independent risk factors for the 6-month mortality. Conclusion: The previous definition of hyperuricemia was not suitable for risk assessment in patients with IE because of the U-shaped relationship between UA levels and in-hospital death. Low and high levels of UA were predictive of increased short-term mortality in IE patients.

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis.

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

Alteration of normal level of serum urate may contribute to decrease in estimated glomerular filtration rate decline in healthy Japanese men.

INTRODUCTION: Serum uric acid (SUA) levels have a linear relationship with the estimated glomerular filtration rate (eGFR). It is unclear whether further changes, subsequent to normal level of SUA can attenuate eGFR decline in a healthy population, so we aimed to determine the normal level of SUA that can contribute to preventing kidney dysfunction. METHODS: In this retrospective cohort study from Japan, annual health checkup data from 2009 to 2014 was collected. After propensity score matching (1:1), data from 2,634 individuals with basal SUA ≤7.0 mg/dL (normal; mean age, 39 y; mean eGFR, 80.8 mL/min/1.73 m2) and 1,642 individuals with basal SUA >7.0 mg/dL (elevated; mean age, 42 y; mean eGFR, 75.0 mL/min/1.73 m2) were collected to determine the relationship between followed-up SUA level and the rate of change in eGFR. RESULTS: In individuals with normal level SUA at baseline, the elevation of SUA (>7.0 mg/dL) accelerated eGFR decline compared to those with normal SUA levels at 5-year follow-up (-4.1 ± 9.6% vs -9.9 ± 9.0%, p < .0001). Digression of SUA level (≤7.0 mg/dL) reduced eGFR decline compared with persistent SUA level over 7.0 mg/dL (-1.5 ± 11.5% vs -7.0 ± 10.1, p < .0001). In multiple linear regression analysis, there was strong association between the rate of change in SUA and eGFR in individuals with basal SUA ≤7.0 and >7.0 mg/dL (standardized coefficient; -0.3348, p < .001 and -.2523, p < .001, respectively). CONCLUSION: Subsequent to normal level of SUA (under 7.0 mg/dL) may contribute to a decrease in eGFR decline in apparently healthy men.

Assessment of the relationship between serum uric acid levels and liver enzymes activity in Bangladeshi adults.

Serum uric acid (SUA) level has been suggested to be associated with cardiovascular disease, diabetes and metabolic syndrome. However, little is known about the relationship between SUA and liver enzymes activity in the general population. The present study aimed to assess the relationship between SUA and serum liver enzymes in an adult population in Bangladesh. In this cross-sectional study, a total of 410 blood samples were collected from apparently healthy adults aged > 18 years. SUA, liver enzymes, lipid profile and other biochemical markers were measured in the collected samples by using standard methods. Multinomial logistic regression model was used to assess the relationship between SUA and elevated levels of liver enzymes among the participants. Overall, the prevalence of hyperuricemia was 30.1% with 32.2% in male and 18.6% in female participants. About 33% of the participants had at least one or more elevated levels of liver enzymes. The mean level of SUA was significantly higher in males (389.3 ± 96.9 µmol/L) than in the female (290.4 ± 89.8 µmol/L) subjects (p < 0.001). There was a significant difference in the mean levels of serum ALT and GGT between the male (34.5 ± 16.0 U/L and 26.7 ± 19.5 U/L, respectively) and female (25.0 ± 13.0 U/L and 19.5 ± 13.2 U/L, respectively) participants (p < 0.001 and p < 0.01, respectively). An increasing trend was observed in the mean levels of serum ALT and GGT across the SUA quartile groups (p < 0.001 and p < 0.01, respectively). SUA showed a positive and significant correlation with serum ALT (p < 0.001) and GGT (p < 0.01). In further statistical analysis after adjustment for potential confounders, SUA showed an independent and significant association with serum ALT and GGT in all regression models. In conclusion, SUA was strongly associated with serum levels of ALT and GGT after adjustment for potential confounders. More prospective studies are needed to clarify the complex relationship between SUA and liver enzymes in the general population.

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats.

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1ß levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Clinical characteristics of cardiovascular patients with extremely low levels of high-density lipoprotein cholesterol.

BACKGROUND: Extremely low levels of high-density lipoprotein cholesterol (HDL-C) are related to high cardiovascular mortality. The underlying mechanism is not well known. This research aims to study the clinical characteristics of cardiovascular patients with extremely low levels of HDL-C. METHODS: All cardiovascular patients in a single Chinese cardiology center that were admitted from January to December 2019 were reviewed. The clinical characteristics of those with HDL-C<20 mg/dL were investigated. RESULTS: A total of 20,655 individuals were enrolled. Of these, 52.17 % were males, and the average age was 58.20 ± 12.98 years old. The prevalence of HDL-C<20 mg/dL was 0.47 % for all patients (N=98) and 1.05 % for inpatients. Of those with HDL-C<20 mg/dL, 88.8 % were inpatients, and 77.6 % were males. Their average age was 60.7 ± 15.1 years. Compared with matched patients with normal HDL-C, systemic inflammation (OR= 5.556, 95% CI 2.798-11.030), hypoalbuminemia (OR=5.714, 95% CI 2.702-12.085), hyperuricemia (OR=5.156, 95% CI 2.560-10.386), low T3 syndrome (OR=4.278, 95% CI 1.627-11.245), anemia (OR=3.577, 95% CI 1.680-7.617), diabetes (OR=3.534, 95% CI 1.693-7.376) and hypertriglyceridemia (OR=2.493, 95% CI 1.264-4.918) were identified as adverse concomitant factors of extremely low HDL-C. HDL-C levels were inversely correlated with the total risk scores in patients with HDL-C<20 mg/dL (r=-0.381, P<0.001) and more significantly correlated in patients with HDL-C<15 mg/dL (r=-0.511, P=0.004). CONCLUSIONS: Extremely low levels of HDL-C tend to occur more frequently in males, older individuals and inpatients. For cardiovascular patients, extremely low levels of HDL-C are usually due to the presence of multiple adverse factors with relatively severe conditions. This could explain the high cardiovascular mortality of individuals with extremely low levels of HDL-C.

High-level uric acid in asymptomatic hyperuricemia could be an isolated risk factor of cardio-cerebrovascular diseases: A prospective cohort study.

BACKGROUND AND AIMS: Whether the asymptomatic hyperuricemia (AH) raise the cardiovascular disease risk with or without hyperuricemia-related comorbidities still remains contentious. Our study was aimed to quantitatively access the incidence risk of coronary heart disease (CHD) and stroke associated with AH. METHODS AND RESULTS: In this prospective cohort study, multivariate-adjusted Cox regression models were applied to evaluate the risk of cardiovascular disease (CVD). Baseline serum uric acid beyond normouricemia (357 mmol/L) was quarterly stratified based on the distribution of healthy populations without CVD onset. 1062 CVD first-attack cases were collected among the 29,974 study population (age range: 18-91, mean age: 47.2 ± 13.9 years-old) with a mean follow-up duration of 5.78 ± 0.83 years. The AH showed overall non-association with the CVD incident. However, significantly increased adjusted hazard ratio (HR) of CVD with 95% confidence interval (CI) were observed when the fourth quartile compared with normouricemia stratum in the total cohort population (CHD: 1.42, 1.21-1.68; stroke: 1.27, 1.06-1.41), male (CHD: 1.26, 1.12-1.55), female (CHD: 1.34, 1.04-2.02; stroke: 2.06, 1.13-3.77) and aged over 50 years-old population. Meanwhile, the age-standardized incidence rate of CVD in the fourth quartile was 2-3 times higher than the normouricemia population. After excluded 14,464 baseline population with diabetes, dyslipidemia, and hypertension, consistent results were also observed in the AH population in absence of comorbidities (CHD: 1.51, 1.22-2.25; stroke: 1.68, 1.13-2.39). CONCLUSION: Asymptomatic hyperuricemia patients exposed to a higher level of uric acid (>=428 mmol/L) could significantly increase the incidence risk of CHD and stroke, with or without hyperuricemia-related comorbidities.

Increase of serum uric acid levels associated with APOE ε2 haplotype: a clinico-genetic investigation and in vivo approach.

Elevated serum uric acid (SUA)-hyperuricemia-is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is associated with both gout and metabolic diseases. Several studies have reported relationships between apolipoprotein E (APOE) haplotypes and SUA levels in humans; however, their results remain inconsistent. This prompted us to investigate the relationship between APOE polymorphisms and SUA levels. Our subjects were 5,272 Japanese men, premenopausal women, and postmenopausal women. Multiple linear regression analyses revealed the ε2 haplotype of APOE to be independently associated with higher SUA in men (N = 1,726) and postmenopausal women (N = 1,753), but not in premenopausal women (N = 1,793). In contrast, the ε4 haplotype was little related to SUA levels in each group. Moreover, to examine the effect of Apoe deficiency on SUA levels, we conducted animal experiments using Apoe knockout mice, which mimics ε2/ε2 carriers. We found that SUA levels in Apoe knockout mice were significantly higher than those in wild-type mice, which is consistent with the SUA-raising effect of the ε2 haplotype observed in our clinico-genetic analyses. Further analyses suggested that renal rather than intestinal underexcretion of urate could be involved in Apoe deficiency-related SUA increase. In conclusion, we successfully demonstrated that the ε2 haplotype, but not the ε4 haplotype, increases SUA levels. These findings will improve our understanding of genetic factors affecting SUA levels.

Evaluation of uric acid disorders and associated factors in essential hypertensive patients at Wolkite University specialized hospital, Southern Ethiopia.

BACKGROUND: Essential hypertension is a condition characterized by a rise in blood pressure of undetermined cause, includes 90% of all hypertensive cases and is a highly important public health challenge with major modifiable cause of morbidity and mortality. Uric acids disorders in particular hyperuricemia are significant problems in essential hypertensive patients and can cause substantial morbidity and mortality. Determination of uric acid disorders may play a major role in the management and early aversion of complications in hypertensive patient. Therefore, this study aimed to determine uric acid disorders and associated factors among essential hypertensive adults in the outpatient department at Wolkite University specialized Hospital, Southern Ethiopia from November 1 to February 30, 2021. METHODS AND MATERIALS: An institional based cross sectional study was conducted on 270 essential hypertensive adults on follow-up in outpatient department from November 1 to February 30, 2021. Structured questionnaires through face to face interviews and participants' medical records were used to collect information on determinants related with uric acid disorders. The blood specimen was collected and level of serum uric acid, blood sugar and lipid profile was measured using standard principles and procedures with an ABX Pentra 400 automated chemistry analyzer. Bivariate and multivariate logistic regression analyses were done to identify factors associated with hyperuricemia. The p-value was set at <0.05 with a 95% confidence interval of the adjusted odds ratio. RESULTS: A total of 270 adult essential hypertensive patients were participated in the study, among those 196(27.4%) of study participants were hyperuricemic with 95%CI (21.9, 33.3). Being alcoholic [(AOR: 15.68, 95% CI: (5.93, 21.41)], taking antihypertensive medication [(AOR: 11.56, 95% CI: (3.94, 23.80)], BMI > = 30 [(AOR: 4.89, 95% CI: (1.46, 25.5)] and being centrally obese [(AOR: 6.87, 95% CI: (2.53, 18.63)] were factors significantly associated with hyperuricemia. CONCLUSION: In this study, the high burden of hyperuricemia (27.4%) was observed in essential hypertensive patients with follow-up in outpatient department. Taking alcohol and antihypertensive medication, being overweight and centrally obese were identified factors of uric acid disorders. The finding of this study should be taken into consideration to implement preventive interventions on identified predictors in hypertensive patients. Taking fruit and vegetable, and promoting physical exercise and determinations of serum uric acid level in adult essential hypertensive patients was recommended to minimize the emergence of hyperuricemia.

Positive association between body fat percentage and hyperuricemia in patients with hypertension: The China H-type hypertension registry study.

BACKGROUND AND AIMS: The relationship between the body fat percentage (BFP) and hyperuricemia is still unknown in different gender subjects. The purpose of this study was to determine the magnitude of the association between the BFP and the presence of hyperuricemia in the sex-specific group among hypertensive patients. METHODS AND RESULTS: We conducted a cross-sectional study enrolling 14,234 hypertensive participates from the Chinese Hypertension Registry Study. Body fat percentage (BFP) was calculated by simple anthropometric parameters. Hyperuricemia was defined as serum uric acid (SUA) level 420 umol/L in men and 360 umol/L in women. The mean BFP was 24.5% in men and 37.1% in women. Multiple logistic analyses showed that the relationship between BFP with the risk of hyperuricemia in a dose-dependent manner among both men (odds ratio [OR] 1.07, 95% CI 1.06, 1.09) and women (OR 1.08, 95% CI 1.06, 1.09) in the fully adjusted model. Subgroup analyses showed the positive association between BFP and the risk of hyperuricemia was consistent in all stratification subgroups (all P for interaction >0.05). CONCLUSION: For patients with hypertension, BFP was positively associated with an increased risk of hyperuricemia among both men and women.