Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

An oral fat-load test was carried out in patients with non-insulin-dependent diabetes mellitus (NIDDM) and angiographically verified coronary artery disease (CAD; group 1, n = 6); in patients with CAD but no diabetes (group 2, n = 6); in patients with NIDDM but no CAD (group 3, n = 4); and in healthy control subjects (group 4, n = 4). Concentrations of apolipoprotein (apo) E, apo C-II, triglyceride (TG), retinyl palmitate, and cholesterol were measured in fasting plasma and in plasma obtained after 2, 4, 6, 9, and 24 h after a meal containing 78 g of fat and 345,000 IU of vitamin A. The same measurements were carried out in the lipoprotein fractions with Svedberg flotation rates Sf 400-1100, 60-400, 20-60 and 12-20, obtained by density gradient ultracentrifugation. The postprandial apo E concentrations were highest in group 1 (NIDDM and CAD) in plasma and in the TG-rich lipoprotein fractions, with significant differences in comparison with the healthy subjects. As shown by apo E to TG ratios, the postprandial lipoproteins were enriched with apo E in the patients with NIDDM and CAD. The largest excesses of apo E in group 1 patients were observed in the atherogenic Sf 12-60 lipoproteins. Across the entire study population, there was a significant inverse correlation between the postprandial apo E responses and the postheparin lipoprotein lipase activity. The results suggest that enrichment of the remnant lipoproteins with apo E may have a role in the increased risk of CAD among patients with NIDDM.
...
PMID:Enrichment with apolipoprotein E characterizes postprandial TG-rich lipoproteins in patients with non-insulin-dependent diabetes mellitus and coronary artery disease: a preliminary report. 815 85

Because remnants of triglyceride-rich lipoproteins (TRLP) are potentially atherogenic, the postprandial lipoprotein metabolism was studied in 12 normocholesterolemic, normotriglyceridemic women, aged 60 +/- 2 years, with angiographically proven coronary artery disease (CAD+; cholesterol 5.7 +/- 0.1 (S.E.) mmol/l, triglyceride 1.35 +/- 0.10 mmol/l) and in 12 individually matched controls, aged 59 +/- 2 years, without angiographical abnormalities (CAD-; cholesterol 5.1 +/- 0.2 mmol/l and triglyceride 1.16 +/- 0.13 mmol/l). Following an oral retinyl palmitate-fat load, the CAD+ women showed a significantly higher triglyceride response in the chylomicron, or Sf > 1000, fraction (P < 0.05 vs. controls). Total plasma apolipoprotein (apo) B and retinyl palmitate concentrations were similar in both groups. Fasting apo B-48 levels in the d < 1.006 g/ml fraction were significantly higher in CAD+ cases (0.25 +/- 0.03 integrated optical density (iod) units) than CAD- controls (0.15 +/- 0.03; P < 0.05). Furthermore, after the fat load, a greater absolute and incremental apo B-48 response in the intermediate density lipoprotein (IDL) fraction (d = 1.006-1.019 g/ml) was observed in CAD+ cases (incremental area under the curve (Delta-AUC)8: 0.40 +/- 0.12 h.iod) than CAD- controls (0.01 +/- 0.06 h.iod; P = 0.01). Post-heparin hepatic lipase (HL) activities were higher in the CAD+ group: 422 +/- 22 mU/l vs 288 +/- 20 mU/ml in the CAD- group (P < 0.001) while lipoprotein lipase (LPL) activities were identical. The results provide evidence that the metabolism of intestinal TRLP is significantly different in normolipidemic women with angiographically proven CAD compared with individually matched controls without coronary disease. Fasting apo B-48 levels in d< 1.006 g/ml fractions represent a potentially useful marker in women at risk for CAD.
...
PMID:Abnormal postprandial apolipoprotein B-48 and triglyceride responses in normolipidemic women with greater than 70% stenotic coronary artery disease: a case-control study. 883 Sep 35

Chylomicron catabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. In rats, triglyceride-rich emulsions can mimic chylomicron metabolism. To further validate this model in man, the emulsion was injected intravenously into fasting and into subjects previously fed a test fatty meal. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined. The fractional clearance rate (FCR) of both labels was markedly reduced in the fed subjects (triglycerides: fed = 0.018 +/- 0.007; fasting = 0.105 +/- 0.013 min-1, P < 0.001; cholesteryl ester: fed = 0.016 +/- 0.001; fasting = 0.040 +/- 0.006 min-1; P < 0.05) indicating that the emulsion and chylomicrons generated from the testinal lipid absorption compete for the same catabolic processes, confirming the validity of the method. The emulsion was injected into 11 patients with CAD and into 11 controls. All had plasma cholesterol < 240 and triglycerides < 250 mg/dl. FCR of triglycerides was 5-fold smaller in CAD compared to controls (0.028 +/- 0.004 and 0.141 +/- 0.069 min-1, respectively, P < 0.01). FCR of cholesteryl ester was 4-fold smaller in CAD than in controls (0.015 +/- 0.004 and 0.056 +/- 0.067 min-1 respectively, P < 0.05). These results indicate that both chylomicron lipolysis and remnant removal are diminished in CAD.
...
PMID:Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease. 887 30

This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups of healthy men with low-, middle-, and upper-decile HDL cholesterol. The number of carriers of the 447stop allele was significantly greater in the high HDL group than in either the groups with normal HDL (P = .017) or low HDL (P < .0001). Additional functional assessment of this mutation did not reveal distinct differences between wild-type LPL and the LPL447stop protein. In conclusion, we have shown that the 447stop mutation is associated with increased HDL cholesterol in healthy Dutch males, although the underlying mechanism remains to be elucidated. Because HDL cholesterol is strongly inversely related with CAD, this genotype might be of potential benefit to its carriers.
...
PMID:Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males. 910 82

The accrued evidence that lipid-lowering therapy limits the progression of atherosclerosis and reduces CAD events is overwhelming. The focus has been on LDL-C reduction with statins, but recent evidence also stresses the importance of raising HDL-C and reducing triglyceride-rich lipoproteins (TRL). Treatment should take into account the type of dyslipidemia, combination therapy, drug interactions and pleiotropic effects of drugs (multiple effects in different systems). Statins and fibrates are the most widely prescribed. Fibrates have a major impact on plasma TRL and HDL-C levels. They enhance lipoprotein lipase, apoAI and apoAII transcription and reduce that of apoCIII. The discovery that their multiple actions are in large part mediated by the PPAR alpha pathway is a breakthrough. Fibrates also lower plasma fibrinogen and plasma viscosity but their ability to inhibit smooth muscle cell activation is one of their most promising pleiotropic effects. Statins are safe and potent LDL-C-lowering agents but also lower TRL and raise HDL. Their pleiotropic effects are numerous, and include vasodilatory, anti-thrombotic, antioxidant, anti-proliferative, anti-inflammatory and plaque stabilizing properties. Many findings make a case for their early use in CAD to improve myocardial perfusion after a myocardial infarction, and they are indicated in heart transplant recipients to improve survival and reduce graft rejection. Fibrates and statins have complementary lipid modifying and pleiotropic effects so that their combination, carried out with caution to avoid potential untoward effects, should provide the highest cardiovascular benefit. This hypothesis is currently being tested in the Lipid in Diabetes Study (LDS), an outcome trial comparing monotherapy with fenofibrate and cerivastatin to combination therapy conducted in England.
...
PMID:Advances in lipid-lowering therapy in atherosclerosis. 1190 Apr 1

A sample of 243 Italian patients affected by the sporadic late-onset form of Alzheimer's disease (AD) was studied for the HindIII intronic polymorphism of the lipoprotein lipase (LPL) gene and compared with a sample of 148 healthy subjects. Since this polymorphism has been reported to be associated with CAD and because the two pathologies share common aspects, we decided to study it in AD too. We found a difference in the allele distribution, in that the H+ allele was more frequent in patients (0.782) than in controls (0.720); this difference was not quite significant (P = 0.059). The odds ratio from the logistic regression analysis for the H+ carrying genotypes was 2.7 (95% CI = 1.01-7.21; P = 0.048). When the separate genotypes H+H+ and H+H- were entered into the analysis, only H+H+ was found to significantly increase the risk with respect to H-H- (P = 0.029). This means that carrying this allele significantly increases the risk of developing AD, and the risk is mostly associated with the H+H+ genotype.
...
PMID:The H+ allele of the lipoprotein lipase (LPL) HindIII intronic polymorphism and the risk for sporadic late-onset Alzheimer's disease. 1533 Nov 47

This study was performed to assess the effect of the S447X and Hind III lipoprotein lipase gene polymorphisms on development of coronary artery disease and hypertriglyceridemia. The study included 132 patients and 98 healthy control subjects of Croatian descent. The lipoprotein lipase S447X polymorphism was associated with coronary artery disease and hypertriglyceridemia, as indicated by the lower frequency of S447 allele in the patient group (p = 0.005) and odds ratio (O.R = 0.40, p = 0.006). The patient and control groups also showed a significant difference in the distribution of Hind III/S447X genotype combinations (p = 0.013). There were no significant associations with lipid parameters for any genotype or genotype combination in the patient group. Frequencies of the S447X polymorphism and S447X/Hind III combinations differed between the CAD/TG and control group, thus these polymorphisms may be associated with CAD and hypertriglyceridemia.
...
PMID:Association of two genetic variations of lipoprotein lipase, S447X and Hind III, with coronary artery disease and hypertriglyceridemia. 1705 22

Recent research has demonstrated a strong genetic linkage between premature coronary artery disease (pCAD) and dyslipidemia. Genetic variation in lipid metabolism can lead to impediment of lipid anabolism and catabolism, which promotes vascular arterosclerogenesis. Currently, related studies were focused on: (1) Gene mutations related to low density lipoprotein metabolism, such as low density lipoprotein receptor, apolipoprotein B, apolipoprotein E; (2) Gene mutations related to high density lipoprotein metabolism-related genes, such as ATP binding cassette transporter, apolipoprotein A1, lipoprotein lipase; (3) low density lipoprotein receptor-related genes: Adiponectin. These genes had been proved to be cor-related with pCAD. Mutations of these genes can lead to series of genetic disease characterized by pCAD. This review gives a brief summary of the roles of these genes played in the initiation and development of pCAD, providing valuable information to primer prevention and individualized treatment of CAD.
...
PMID:[Research progress on the association between genetic variations in lipid metabolism and premature coronary artery disease]. 1855 Apr 87

---