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)

Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T-455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T-455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the -455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the -455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.
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PMID:Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. 1456 27

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.
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PMID:Analysis of candidate genes in Polish families with obesity. 1520 83

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.
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PMID:Role of fibric acid derivatives in the management of risk factors for coronary heart disease. 1545 34

Triglyceride-rich lipoproteins contain both apolipoproteins E (ApoE) and C-III (ApoC-III), which show opposite functional properties. The relationships between the ApoE (epsilon2/epsilon3/epsilon4) gene polymorphism and ApoC-III/ApoE ratio has never been investigated. A large population (n=552) of cardiovascular patients, without diabetes and/or lipid-lowering therapy, with or without metabolic syndrome (MetSyn), was genotyped for epsilon2/epsilon3/epsilon4 polymorphism and their ApoCIII/ApoE ratio was evaluated. A second group of patients (n=76) with peripheral artery disease was also genotyped and their ApoC-III/ApoE ratios were measured in HDL and non-HDL fractions. Subjects with E2 had higher and E4 carriers lower TG,ApoE and ApoC-III levels, respectively. The ApoCIII/ ApoE ratio showed an opposite trend, gradually increasing from E2/E2 to E4/E4 subjects. MetSyn patients also had an elevated ApoC-III/ApoE ratio and E4 carriers were more frequent in MetSyn patients (OR 2.08 with a 95%CI 1.22-3.5). The distribution of ApoC-III/ApoE ratio was confirmed also in the second group, with lower values in E2/E3 and higher in E3/E4 subjects. Similar results were obtained for the concentrations measured in non-HDL fractions, but not in the HDL fractions. ApoE epsilon2/epsilon3/epsilon4 gene polymorphism is a determinant of the relative proportion of apolipoprotein C-III to E. Carriers of the unfavourable E4 allele present the highest ApoCIII/ApoE ratio and are twofold more frequent among individuals affected by MetSyn.
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PMID:ApoE epsilon2/epsilon3/epsilon4 polymorphism, ApoC-III/ApoE ratio and metabolic syndrome. 1818 30

The concurrence of visceral obesity, insulin resistance and dyslipidaemia comprises the concept of the metabolic syndrome. The metabolic syndrome is an escalating problem in developed and developing societies that tracks with the obesity epidemic. Dyslipidaemia in the metabolic syndrome is potently atherogenic and, hence, is a major risk factor for CVD (cardiovascular disease) in these subjects. It is globally characterized by hypertriglyceridaemia, near normal LDL (low-density lipoprotein)-cholesterol and low plasma HDL (high-density lipoprotein)-cholesterol. ApoC-III (apolipoprotein C-III), an important regulator of lipoprotein metabolism, is strongly associated with hypertriglyceridaemia and the progression of CVD. ApoC-III impairs the lipolysis of TRLs [triacylglycerol (triglyceride)-rich lipoproteins] by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. In the circulation, apoC-III is associated with TRLs and HDL, and freely exchanges among these lipoprotein particle systems. However, to fully understand the complex physiology and pathophysiology requires the application of tracer methodology and mathematical modelling. In addition, experimental evidence shows that apoC-III may also have a direct role in atherosclerosis. In the metabolic syndrome, increased apoC-III concentration, resulting from hepatic overproduction of VLDL (very-LDL) apoC-III, is strongly associated with delayed catabolism of triacylglycerols and TRLs. Several therapies pertinent to the metabolic syndrome, such as PPAR (peroxisome-proliferator-activated receptor) agonists and statins, can regulate apoC-III transport in the metabolic syndrome. Regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidaemia and CVD risk in the metabolic syndrome.
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PMID:Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. 1839 97