Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased serum urate concentration is a frequent finding in patients with hypertension. Since hyperuricemia is associated with obesity, renal disease, hyperlipidemia, and atherosclerosis, whether or not serum urate is a cardiovascular risk factor per se has remained elusive. The subjects were 210 Turkish male and 210 female adults over 20 years of age. None had diabetes mellitus, endocrine diseases, or renal or hepatic disease, and those receiving antihypertensive drugs, systemic corticosteroids, or lipid-lowering drugs were excluded. Height, weight, blood pressure, serum glucose, lipid profiles, serum insulin, DHEA-SO4, and leptin were measured in the morning after an overnight fast. Women had significantly higher mean leptin (20.3 +/- 0.88 ng/mL vs 5.78 +/- 0.39 ng/mL, P < 0.001) and lower mean uric acid (248.03 +/- 4.76 micromol/L vs 311.6 +/- 5.35 micromol/L, P < 0.001), triglyceride (1.42 +/- 0.06 mmol/L vs 1.61 +/- 0.06 mmol/L, P < 0.001), and DHEA-SO4 (3.02 +/- 0.17 micromol/L vs 4.43 +/- 0.19 micromol/L, P < 0.001) concentrations than men, even when adjusted for BMI. On univariate correlation analysis, leptin showed the strongest association with BMI in both sexes and also correlated significantly with BMI, insulin, uric acid, glucose, total cholesterol, and triglycerides in males and BMI, insulin, uric acid, total cholesterol, apo B, and creatinine in females after adjustment for age and BMI. A statistical model containing creatinine, leptin, insulin, and triglycerides accounted for 34% of the variance in serum uric acid levels in men, whereas another consisting of creatinine, triglycerides, leptin, SBP, and insulin explained 42% of the variance in serum uric acid in women. The present study suggests that leptin could be one of the possible candidates for the missing link between obesity and hyperuricemia. Our study may also suggest that hyperuricemia is not only a metabolic end product but also a marker of a major pressor or pathogenic mechanism underlying the hypertension in obesity.
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PMID:Leptin might be a regulator of serum uric acid concentrations in humans. 1290 34

Hyperinsulinemia is a marker of insulin resistance, a correlate of the metabolic syndrome, and an established precursor of type 2 diabetes. This US study investigated the role of risk factors associated with hyperinsulinemia in cross-sectional studies in progression to incident hyperinsulinemia. Nondiabetic participants from the Atherosclerosis Risk in Communities Study (n = 9,020) were followed from 1987 to 1998 for the development of hyperinsulinemia (fasting serum insulin > or = 90th percentile, 19.1 micro U/ml). After adjustment for demographic characteristics, all risk factors simultaneously, and baseline insulin value, the risk of progressing to hyperinsulinemia increased per standard deviation increase in baseline uric acid (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.2, 1.4; per 1.4 mg/dl) and waist/hip ratio (OR = 1.4, 95% CI: 1.2, 1.5; per 0.08) and was inversely associated with high density lipoprotein cholesterol (OR = 0.8, 95% CI: 0.7, 0.9; per 0.4 mmol/liter). Starting to smoke (OR = 1.5, 95% CI: 1.2, 2.0) and becoming obese (OR = 2.4, 95% CI: 1.8, 3.1) during the study were also associated with increased risk. The associations were similar across race and gender groups. These data suggest that, in addition to weight gain, hyperuricemia, dyslipidemia, and smoking can be detected prior to development of hyperinsulinemia.
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PMID:Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987-1998. 1463 Jun 1

A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G --> T (Val279Phe) in the platelet-activating factor acetylhydrolase gene, 242C --> T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C --> T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia.
Atherosclerosis 2004 Jan
PMID:Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia. 1470 72

Plain old balloon angioplasty (POBA) is a useful therapeutic strategy especially for angioplasty of small coronary arteries. An association study was performed to identify genes that confer susceptibility to restenosis after POBA. The study population comprised 730 individuals (424 men, 306 women) who underwent successful POBA in at least one major coronary artery and were examined angiographically 6 months after the procedure. A total of 469 subjects (273 men, 196 women) exhibited no restenosis after POBA for any of the coronary lesions, whereas 261 subjects (151 men, 110 women) manifested restenosis for all lesions. The genotypes for 40 polymorphisms of 34 genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that two polymorphisms (242C --> T in the NADH/NADPH oxidase p22 phox (p22-PHOX) gene and 2136C --> T in the thrombomodulin (THBD) gene) in men and two polymorphisms (584G --> A in the paraoxonase 1 (PON1) gene and 2445G --> A in the fatty acid-binding protein 2 (FABP2) gene) in women were significantly associated with restenosis after POBA. A stepwise forward selection procedure revealed that the effects of these polymorphisms on restenosis were statistically independent of conventional risk factors for coronary artery disease. Genotyping of these polymorphisms may prove informative for assessment of genetic risk for restenosis after POBA.
Atherosclerosis 2004 May
PMID:Genetic risk for restenosis after coronary balloon angioplasty. 1513 68

Because mitochondria are the major sources of reactive oxygen species (ROS) in cells, certain alterations in mitochondrial functions can lead to metabolic perturbation in vascular endothelial cells and smooth muscle cells, resulting in vascular dysfunction. We previously demonstrated that a C --> A transversion in mitochondrial DNA (mtDNA) at nucleotide 5178 of the NADH dehydrogenase subunit 2 (ND2) gene, which results in a Lue --> Met substitution at amino acid 237, was found more frequently in Japanese centenarians than in controls. We also demonstrated that this Mt5178C --> A polymorphism has anti-atherosclerotic effects in diabetic subjects. We have now examined whether the Mt5178C --> A (Leu237Met) polymorphism in the mitochondrial ND2 gene is associated with a low prevalence of myocardial infarction (MI) in a case-control study. The genotype of ND2 gene was determined either with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or a colorimetry-based allele-specific DNA probe assay. Multivariate logistic regression analysis with adjustment for age, gender, body mass index, smoking status, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that the frequency of the Mt5178A genotype was significantly higher in controls than in subjects with MI. These results suggest that the 5178A genotype of mitochondrial ND2 gene polymorphism is protective against MI; and this effect would explain, at least in part, its contribution to longevity.
Atherosclerosis 2004 Aug
PMID:Association of a 5178C-->A (Leu237Met) polymorphism in the mitochondrial DNA with a low prevalence of myocardial infarction in Japanese individuals. 1526 84

Two hundred and sixty two patients with clinical diagnosis of permanent ischemic stroke, all of them aged 60 or more were retrospectively studied from the 1015 cerebrovascular diseases (CVD) records of the Atherosclerosis League of the Neurology Clinics of the ISCMSP, from 1990 to 2002. The study emphasized modifiable risk factors frequencies for ischemic stroke in this population, considering gender and age of the patients. Results have evidenced that systemic arterial hypertension is a main risk factor significantly frequent in old people (87.8%), independently of gender and age. Smoking (46.9%) and alcohol consumption (35.1%) have revealed to be very frequent important modifiable risk factors especially among men. Lower frequencies have been presented for cardiac diseases (27.0%), Diabetes Mellitus (19.9%), and dyslipidemia (15.6%) as risk factors for ischemic stroke in old people of both genders and all ages after 60. There was relatively low frequency of hyperuricemia in this set of patients.
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PMID:[Study of the main risk factors frequencies for ischemic cerebrovascular disease in elderly patients]. 1547 81

Recent experimental findings have led to renewed interest in the possible role of uric acid in the pathogenesis of both hypertension and vascular disease. Often considered an antioxidant, biochemical and in vitro data indicate that noncrystalline, soluble uric acid also can react to form radicals, increase lipid oxidation, and induce various pro-oxidant effects in vascular cells. In vitro and in vivo findings suggest that uric acid may contribute to endothelial dysfunction by inducing antiproliferative effects on endothelium and impairing nitric oxide production. Proinflammatory and proliferative effects of soluble uric acid have been described on vascular smooth muscle cells (VSMCs), and in animal models of mild hyperuricemia, hypertension develops in association with intrarenal vascular disease. Possible adverse effects of uric acid on the vasculature have been linked to increased chemokine and cytokine expression, induction of the renin-angiotensin system, and to increased vascular C-reactive protein (CRP) expression. Experimental evidence suggests a complex but potentially direct causal role for uric acid in the pathogenesis of hypertension and atherosclerosis.
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PMID:Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. 1566 Mar 33

Little is known about uric acid role for cardiovascular events in the Asian-Pacific countries with relatively low coronary heart disease (CHD) but high stroke events. Also, there is scanty evidence for repeated measures of uric acid levels among population. We examined associations of basic and repeated measures of uric acid level with CHD and stroke events in one Taiwanese adult community prospectively. Cox proportional hazards models, treating uric acid as baseline and time-dependent covariates, were used to assess the 11-year risk of CHD and stroke events. Among 3602 adult subjects older than 35 years, 86 incident CHD and 155 incident stroke cases were identified. The rate ratios of hyperuricemia ranged between 2.00 and 3.96, with higher risk ratios in women than in men. The rate differences and population attributable fractions were also higher in women than in men, implying that women had high risk of uric acid on cardiovascular events. After adjustment for age effect, time-dependent uric acid was associated with significant CHD risk in both genders (hazard risk [HR] 1.43, 95% CI: 1.10-1.87 in men and HR 1.22, 95% CI: 1.03-1.44 in women). But the magnitude of hazard risks decreased after adjusting more atherosclerotic risk factors for CHD. For stroke event, the age-adjusted hazard risk of time-dependent continuous uric acid level was 1.23 (95% CI: 1.00-1.54) in men and 1.36 (95% CI: 1.05-1.75) in women. Multiple adjustment by risk factors demonstrated that uric acid was still a significant predictor for stroke in women (HR 1.32, 95% CI: 1.00-1.73). The similar hazard risk patterns existed for binary categories of hyperuricemia. Subgroup analyses demonstrated uric acid had significant risk only in hypertension and metabolic syndrome subgroups, not in their counterparts. We concluded that uric acid, in the baseline and time-dependent variables, could predict cardiovascular events in the community of relatively low CHD but high stroke risk in Taiwan.
Atherosclerosis 2005 Nov
PMID:Hyperuricemia as a risk factor on cardiovascular events in Taiwan: The Chin-Shan Community Cardiovascular Cohort Study. 1615 34

Since 1967, fructose has become the primary commercial sweetener in the food industry. Large amounts of fructose can be toxic and have been correlated with atherosclerosis, malabsorption, hyperuricemia, lactic acidosis, and cataracts. To understand the deleterious and critical role(s) fructose plays in normal metabolism, it is essential to know how and where fructose is metabolized. The fructose transporter, GLUT5, and the specialized enzymes ketohexokinase, aldolase, and triokinase comprise the well-defined fructose-specific metabolic pathway found in liver, kidney, and small intestine. It is estimated that 50-70% of ingested fructose is metabolized in these tissues; where and how the remaining 30-50% is metabolized is not well defined. Prediction of tissues capable of metabolizing fructose via this pathway was done using expressed sequence tags (ESTs) in Unigene and a gene-specific virtual northern blot (VNB) algorithm. Unigene and VNB combined correctly predicted the expression of the genes required for fructose metabolism in liver, kidney, and small intestine. Both methods indicated brain, breast, lymphocytes, muscle, placenta, and stomach additionally express this set of genes. Expression of the genes for GLUT5 (glut5) and ketohexokinase (khk) in neurons was validated by immunohistochemistry and RNA in situ hybridization, respectively. Using stringent controls, clear expression of glut5 and khk was localized to Purkinje cells in the cerebellum. Cerebellum was used to oxidize fructose to carbon dioxide. Together, these data suggest that these neurons in the brain are able to utilize fructose as a carbon source.
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PMID:Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum. 1626 70

Hyperuricemia is postulated to be a risk factor for atherosclerotic diseases, although whether it is independent of classical atherogenic risk factors is controversial. The automatic computer-assisted measurement of brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible method by which to assess arterial stiffness, a potential surrogate marker of early atherosclerosis. By analyzing cross-sectional data from 982 individuals who underwent health screening, we have investigated whether serum uric acid is associated with high baPWV, which was determined as the highest quartile of baPWV values, in a sex-specific manner. Multivariate analysis showed that the odds ratios (95% CI) of the highest baPWV quartile across the sex-specific quartiles of serum uric acid were 1.0, 2.80 (0.93-8.40), 2.13 (0.74-6.19), and 2.76 (1.01-7.55) in women, and 1.0, 1.10 (0.55-2.20), 1.97 (1.04-3.75), and 2.24 (1.10-4.56) in men after adjusting for age, total and HDL-cholesterol, BMI, systolic blood pressure, triglycerides, fasting glucose and smoking status. The association between uric acid and high baPWV was observed in both subjects with metabolic syndrome and those without. These data suggest that in both genders, serum uric acid level is associated with increased baPWV, a marker of arterial stiffness, and is in part independent of other conventional risk factors for atherosclerosis and metabolic syndrome.
Atherosclerosis 2007 May
PMID:Higher serum uric acid is associated with increased arterial stiffness in Japanese individuals. 1671 28


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