Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In humans, uric acid is the main urinary metabolite of purines. Serum levels are higher compared with other mammalians. Uric acid is an antioxidant and perhaps helps to control blood pressure during a low Na+ diet through stimulation of the renin-angiotensin system. Serum uric acid is also considered a marker of tubular reabsorption and 'effective' circulating blood volume. Moreover, hyperuricemia seems to be a cofactor in Na+ -sensitive hypertension, a marker and possibly itself responsible for microvascular damage through stimulation of the renin-angiotensin system, inhibition of endothelial nitric oxide, and proliferative effects on vascular smooth muscle. As fructose-rich diets increase uric acid levels, hyperuricemia may also play a role in the metabolic syndrome, triggering insulin resistance and hypertension.A number of studies on rats rendered hyperuricemic by administration of uricase inhibitors have recently confirmed induction of arterial hypertension and microvascular injury, particularly in the remnant kidney or in cyclosporine-induced renal fibrosis.
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PMID:Uric acid: bystander or culprit in hypertension and progressive renal disease? 1885 44

The aim of this study was to examine the prevalence of hyperuricemia and its associated factors in an urban area of Izmir, located in western Turkey. Our study group was selected by computerized sampling from the participants of a larger population-based study searching for the prevalence of rheumatoid arthritis in Balcova and Narlidere districts of Izmir. A total of 132 subjects (69 women and 63 men) were included in this study. Serum uric acid, glucose, creatinine and lipid levels were studied. Body composition along with body fat percentage was determined anthropometrically. A total of 16 subjects had hyperuricemia (4 women and 12 men). The overall prevalence of hyperuricemia was 12.1% and the mean uric acid level was 4.9 +/- 1.3 mg/dl. Males had significantly higher uric acid levels than females (P < 0.05; 5.5 +/- 1.3 vs. 4.3 +/- 1.1 mg/dl, respectively). The prevalence of hypertension, diabetes, obesity and metabolic syndrome was 24.4, 5.3, 28 and 26.5%, respectively. There was no gouty subject. Sum of skinfold thickness (SFT) measurements and creatinine levels were the independent predictors of hyperuricemia (beta = 0.45, 0.47, respectively). Uric acid measurement is important not only for inflammatory rheumatic disorders but also for predicting metabolic syndrome and related coronary artery disease. There is sex difference in uric acid levels in favor of women most probably explained by gonadal hormones. Hyperuricemia is significantly predicted by anthropometric measure of SFT which is a simple clinical screening method along with creatinine levels.
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PMID:Hyperuricemia and its related factors in an urban population, Izmir, Turkey. 1904 57

Hyperuricemia is associated with hypertension, metabolic syndrome, preeclampsia, cardio-vascular disease and renal disease, all conditions associated with oxidative stress. We hypothesized that uric acid, a known antioxidant, might become prooxidative following its reaction with oxidants; and, thereby contribute to the pathogenesis of these diseases. Uric acid and 1,3-(15)N(2)-uric acid were reacted with peroxynitrite in different buffers and in the presence of alcohols, antioxidants and in human plasma. The reaction products were identified using liquid chromatography-mass spectrometry (LC-MS) analyses. The reactions generate reactive intermediates that yielded triuret as their final product. We also found that the antioxidant, ascorbate, could partially prevent this reaction. Whereas triuret was preferentially generated by the reactions in aqueous buffers, when uric acid or 1,3-(15)N(2)-uric acid was reacted with peroxynitrite in the presence of alcohols, it yielded alkylated alcohols as the final product. By extension, this reaction can alkylate other biomolecules containing OH groups and others containing labile hydrogens. Triuret was also found to be elevated in the urine of subjects with preeclampsia, a pregnancy-specific hypertensive syndrome that is associated with oxidative stress, whereas very little triuret is produced in normal healthy volunteers. We conclude that under conditions of oxidative stress, uric acid can form reactive intermediates, including potential alkylating species, by reacting with peroxynitrite. These reactive intermediates could possibly explain how uric acid contributes to the pathogenesis of diseases such as the metabolic syndrome and hypertension.
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PMID:Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. 1921 41

Little is known about the interrelationships between metabolic syndrome (MS), uric acid, and early carotid atherosclerosis with diet in adolescents. We investigated associations among diet, carotid intima-media thickness (cIMT), MS, uric acid, and other cardiovascular risk factors in adolescents. Two hundred forty-nine adolescents from 3 high schools in Central California-a predominately Hispanic (n = 119, 16.1 +/- 0.9 years old, 94% Hispanic), a mixed-ethnicity (n = 94, 15.7 +/- 1.2 years old), and a Seventh-day Adventist (SDA) (n = 33, 17.0 +/- 1.3 years old) high school-were assessed for cIMT, blood lipids, uric acid, blood glucose, systolic and diastolic blood pressure, body mass index (BMI), and dietary intake. Compared with SDA adolescents, the predominately Hispanic and mixed-ethnicity high school adolescents exhibited higher low-density lipoprotein and BMI percentile, whereas adolescents from the SDA and mixed-ethnicity high schools exhibited lower uric acid and fasting glucose levels than those from the Hispanic high school. After adjusting for age and sex, cIMT was only correlated with systolic blood pressure percentile (r = 0.16, P < .01). Controlling for age, levels of uric acid were correlated with BMI percentile (males: r = 0.59, P < .001; females: r = 0.24, P < .01), low-density lipoprotein (males: r = 0.40, P < .001; females: r = 0.20, P < .01), and total cholesterol in males (r = 0.38, P < .001). Despite no significant differences in the high school frequency of MS risk factors, 59% of adolescents had one or more MS risk factors. A relationship was noted between the number of MS risk factors and uric acid (P < .002). Most of the adolescents presented MS risk factors independent of ethnicity or a purportedly healthier lifestyle (SDA). Uric acid association with MS and its risk factors suggests its potentially heightened importance for the assessment of adolescent cardiovascular health.
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PMID:Carotid intima-media thickness, dietary intake, and cardiovascular phenotypes in adolescents: relation to metabolic syndrome. 1984 77

Uric acid (UA) is the final catabolic product of purine metabolism and elevated levels are associated with diabetes and cardiovascular disease. A recent meta-analysis of genome-wide association studies totalling 28,141 participants identified five novel loci associated with serum UA levels. In our population-based cohort of 7795 subjects, we replicated four of these five loci; PDZK1 (rs12129861, P = 1.07 x 10(-3)), glucokinase regulator protein (GCKR) (rs780094, P = 4.83 x 10(-4)), SLC16A9 (rs742132, P = 0.047) and SLC22A11 (rs17300741, P = 6.13 x 10(-3)), but not LRRC16A (rs742132, P = 0.645). Serum UA concentration is a complex trait, closely associated to renal UA handling (fractional UA excretion, P < 1 x 10(-300)), renal function (serum creatinine, P < 1 x 10(-300)) and the metabolic syndrome (including fasting insulin, P = 2.48 x 10(-232); insulin resistance, P = 2.51 x 10(-258); waist circumference, P < 1 x 10(-300)) and systolic blood pressure (P = 1.93 x 10(-219)). Together these factors explain 67% of the variance in UA levels. Therefore, we sought to determine the potential contribution of these factors to the association of these novel loci with UA levels, by including them as additional explanatory variables in our analyses, and by considering them as alternative response variables. The association with the GCKR locus is attenuated by serum triglycerides and fractional UA excretion. We also observed the GCKR locus to be associated with total cholesterol (P = 7.52 x 10(-6)), triglycerides (P = 2.65 x 10(-9)), fasting glucose (P = 0.011), fractional UA excretion (P = 3.36 x 10(-5)) and high-sensitive CRP (P = 1.18 x 10(-3)) also after adjusting for serum UA levels. We argue that GCKR locus affects serum UA levels through a factor that also affects triglycerides.
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PMID:Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms. 1986 89

Uric acid is the final product of purine metabolism in human beings. Despite the fact that uric acid was first identified approximately 2 centuries ago, certain pathophysiologic aspects of hyperuricemia are still not clearly understood. For years, hyperuricemia has been identified with or thought to be the same as gout, but uric acid has now been identified as a marker for a number of metabolic and hemodynamic abnormalities.The prevalence of the metabolic syndrome is very high in hyperuricemic patients. Recent epidemiologic studies support the view that asymptomatic hyperuricemia in patients at low cardiovascular risk is likely to result from diminished renal uric acid clearance and to be benign in outcome. In contrast, hyperuricemia in patients at high cardiovascular risk may promote or reflect alternative or additional pathogenetic factors promoting inflammatory, ischaemic or oxidative stresses to the heart and vessels. This hypothesis warrants testing, particularly in carefully designed randomized controlled urate-lowering interventional trials.
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PMID:[Hyperuricemia and the metabolic syndrome]. 2019 66

Urate is produced as the major end product of purine metabolism. In the last decade, the incidence of hyperuricemia increased markedly, and similar trends in the epidemiology of metabolic syndrome have been observed. Hyperuricemia is associated with renal disease, and recent studies have reported that mild hyperuricemia results in hypertension, intrarenal vascular disease, and renal injury. This has led to the hypothesis that uric acid may contribute to renal fibrosis and progressive renal disease. Our purpose was to investigate the relationship between uric acid and renal tubular injury. We applied the method of intraperitoneal injection of uric acid to generate the hyperuricemic mouse model. Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups. In vitro, uric acid significantly induced NRK-52E cells to express the ECM marker fibronectin, as well as LOX, which plays a pivotal role in ECM maturation, in a time- and dose-dependent manner. Upregulation of the urate transporter URAT1, which is located in the apical membrane of proximal tubules, sensitized the uric acid-induced fibronectin and LOX induction, while both knocking down URAT1 expression in tubular epithelial cells by RNA interference and inhibiting URAT1 function pharmacologically attenuated LOX and fibronectin expression. Furthermore, knockdown of LOX expression by a small interfering RNA strategy led to a decrease in fibronectin abundance induced by uric acid treatment. In addition, evidence of a uric acid-induced activation of the NF-kappaB signaling cascade was observed. Our findings highlight a need for carefully reevaluating our previous view on the pathological roles of hyperuricemia in the kidney and nephropathy induced by uric acid in clinical practice.
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PMID:Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells. 2048 95

Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73 m(2) in the former and 609 mg/day/1.73 m(2) in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS.
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PMID:Uric acid metabolism in patients with primary gout and the metabolic syndrome. 2054 16

Hyperuricemia has recently been recognized to not only be a predictor of cardiovascular disease but also a marker of metabolic syndrome. We examined the association between uric acid levels and various clinical parameters, including the components of metabolic syndrome, in essential hypertension. One hundred forty-six untreated Japanese hypertensive patients (mean 58.3 years) without overt cardiovascular disease were divided into low and high uric acid groups by the median uric acid value (cut-off: 6.3 for men and 4.4 mg/dL for women). The high uric acid group had higher serum creatinine (0.74 vs. 0.67 mg/dL, p = 0.019) and a larger body mass index (BMI) (25.2 vs. 23.6 kg/m(2), p = 0.018) compared to the low group. Men from the high uric acid group were younger and had higher blood pressure (BP) than men from the low group. Uric acid levels were correlated with creatinine in both genders, with blood pressure, triglycerides in men only, and with BMI, fasting glucose in women only. Multiple regression analysis also indicated a significant correlation of uric acid with creatinine in both genders, with triglycerides in men, and with glucose in women. Metabolic syndrome (modified NCEP-ATPIII definition) was found in 37.0% of the high uric acid group (men 45.0, women 27.3%) and 20.8% of the low group. Results suggest that an increase of uric acid is associated with impaired renal function and constitutes a risk factor for metabolic syndrome. Uric acid may also be a useful index for initial risk stratification of untreated patients with essential hypertension.
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PMID:Association of uric acid with risk factors for chronic kidney disease and metabolic syndrome in patients with essential hypertension. 2066 27

Data from a cross-sectional population-based study carried out in the town of Bollate (Milan) were used to verify whether there is an age-modulated relationship between the components of blood pressure (BP) and plasma uric acid and fibrinogen levels. Changes in uric acid and fibrinogen levels in relation to diastolic BP (DBP), systolic BP (SBP), mean arterial pressure (MAP) and pulse pressure (PP) in 820 subjects aged 42-59 years and in 509 subjects aged 60-74 years were estimated from general linear models adjusted by the clinical, lifestyle and biological variables traditionally associated with cardiovascular risk. Uric acid levels significantly increased with DBP and MAP only in the middle-aged group without metabolic syndrome or diabetes, and were even in those who were pre-hypertensive. On the contrary, fibrinogen levels significantly increased with SBP and PP only among the elderly with metabolic syndrome or diabetes, and were particularly high among those with stage 2 hypertension. These findings add evidence concerning an age-modulated relationship between the levels of uric acid and fibrinogen and the steady and pulsatile components of BP and it is possibly related to the different mechanisms underlying increased BP: renal factors in middle-aged subjects and vascular abnormalities in the elderly.
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PMID:Uric acid and fibrinogen: age-modulated relationships with blood pressure components. 2086 68


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