Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although lipoprotein(a) [Lp(a)] was first described more than 35 years ago, adequate prospective data have only recently supported Lp(a) as an independent risk factor for coronary heart disease (CHD). In vitro studies suggest that Lp(a) contributes to atherogenesis directly by cholesterol uptake and indirectly by the inhibition of fibrinolysis. In patients with CHD or a significant risk for CHD, Lp(a) should be measured and treated with either niacin or estrogen if the patient has Lp(a) cholesterol levels of more than 10 mg/dL or an Lp(a) mass of more than 30 mg/dL. In addition, homocysteine and remnantlike lipoprotein cholesterol are strongly supported by prospective or population-based prevalence data as independent risk factors for CHD. Homocysteine levels of more than 14 mumol/L should be treated with vitamin supplements of folate, B6, and B12. Remnantlike lipoprotein cholesterol is the product of a novel immunoassay that separates the partially hydrolyzed triglyceride-rich remnant particles. The association of these particles with CHD risk in women may explain the small independent CHD risk that triglycerides have in women in the Framingham Heart Study. A clear therapeutic intervention has not been documented but may include diet, fibric acid derivatives, or hydroxymethylglutamyl coenzyme A reductase inhibitors.
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PMID:Lipoprotein(a), homocysteine, and remnantlike particles: emerging risk factors. 1019 79

The influence of fluvastatin, a liver-selective, competitive inhibitor of the 3-hydroxymethyl-glutaryl-coenzyme A reductase, on the lipoprotein metabolism was investigated in 9 patients with nephrotic syndrome. All patients had biopsy-proven renal disease as cause of their nephrotic syndrome and exhibited severe hyperlipidemia [baseline: serum cholesterol 358 +/- 46 mg/dl (9.3 mmol/l), low-density lipoprotein cholesterol 236 +/- 18 mg/dl (6.1 mmol/l), triglycerides 333 +/- 28 mg/dl (3.8 mmol/l), and lipoprotein Lp(a) 46 +/- 11 mg/dl]. After 1 year of 40 mg of fluvastatin, significant reductions of total cholesterol by 31% to 242 +/- 26 mg/dl (6.3 mmol/l) and low-density lipoprotein cholesterol by 29% to 162 +/- 12 mg/dl (4.2 mmol/l) were observed. Furthermore, triglyceride values were also lowered significantly by 19% to 268 +/- 21 mg/dl (3.1 mmol/l). Lipoprotein Lp(a) and high-density lipoprotein-cholesterol remained unchanged by fluvastatin. These improvements in lipid profile were maintained during the entire follow-up period of 1 year. There were no adverse events, and the slight increase in serum creatinine observed during the study was considered to be due to the primary renal disease. In conclusion, long- term administration of fluvastatin in patients with nephrotic syndrome appears to be an effective and safe treatment of the hyperlipidemia associated with this disorder.
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PMID:Efficiency of 1-year treatment with fluvastatin in hyperlipidemic patients with nephrotic syndrome. 1046 Sep 40

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.
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PMID:Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH). 1099 51

Abnormal lipid and lipoprotein cholesterol values have been defined as a low-density lipoprotein (LDL) cholesterol (C) value of 160 mg/dL (4.1 mmol/L) or greater, a high-density lipoprotein (HDL) C value less than 40 mg/dL (1.0 mmol/L), triglycerides (TG) 150 mg/dL (1.7 mmol/L) or greater, and a lipoprotein (a) (Lp(a)) of 30 mg/dl or greater. Such values all increase coronary heart disease (CHD) risk. The National Cholesterol Education Program Adult Treatment Panel III guidelines continue to focus on optimizing LDL-C values (established as < 100 mg/dL or 2.6 mmol/L), especially in those with established CHD, diabetes, or a 10-year CHD risk over 20%. Dietary saturated fat (< 7% of calories) and cholesterol (< 200 mg/day) restriction, and the use of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the mainstays of treatment in this regard. Such treatment substantially reduces CHD risk. Severe hypertriglyceridemia (> 1000 mg/dL or 11.0 mmol/L) is associated with pancreatitis, and fat restriction, control of glucose, and fibrate therapy are indicated in such patients. Niacin is currently the most effective agent for lowering Lp(a) and raising HDL-C. Current recommendations for treatment by diet and drugs are outlined.
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PMID:Diagnosis and management of lipoprotein abnormalities. 1213 66

Previous studies have shown that homocysteine influences the structure of lipoprotein(a) [Lp(a)] and its affinity to fibrin, and that there is an increased risk of vascular disease when both homocysteine and Lp(a) are elevated. The aim of this study was to determine whether there is a correlation between increased total homocysteine (tHCY) and high Lp(a) concentrations, and whether increased concentrations of tHCY affect the concentration of unbound serum apolipoprotein(a) [Apo(a)]. Forty-seven male subjects recruited from a primary prevention screening program with normal serum creatinine and Lp(a) concentrations above 30 mg/dL were included and underwent a standardized oral methionine-loading test to increase the plasma tHCY concentration. This increase might lead to a modification of the Apo(a) structure, thus possibly influencing the serum concentration of unbound Apo(a). Fasting blood samples were taken before the tests and after 6 hours. The median values of tHCY increased about 4-fold after the methionine-loading test. Fasting tHCY did not show an association with Apo(a) and a post-methionine load increase of unbound Apo(a) was not observed. Backward multiple linear regression analysis, however, revealed that only post-load tHCY was independently and significantly influenced by Lp(a). Furthermore, Lp(a) correlated significantly with post-load tHCY, but not with fasting tHCY. Subdividing the subjects according to the Lp(a) concentration showed a significantly higher median concentration of tHCY after methionine load in subjects with Lp(a) over 50 mg/dL compared to subjects with Lp(a) under 50 mg/dL (P =.009). A similar cut-off was seen for post-load Apo(a) at 7.3 mg/dL (P =.04). Factors such as age, C677T-methylene-tetrahydrofolate-reductase (MTHFR) mutation, folate, vitamin B(12), and creatinine showed no significant influence on post-load tHCY in the different subgroups. The reasons for our findings remain partially unclear. However, considering our results and the current knowledge on the association of tHCY and Lp(a) concentration with the renal function, we hypothesize that both parameters may be linked by commencing renal metabolic dysfunction. It should be stressed that our hypothesis is speculative and that further studies will be necessary to improve the understanding of the interrelation of tHCY and Lp(a) concentration.
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PMID:Post-methionine-load hyperhomocysteinemia and increased lipoprotein(a) are associated with renal metabolic dysfunction: a hypothesis. 1237 Aug 40

Increased blood cholesterol concentration is one of the main factors in ischemic heart disease, development of which is determined by atherosclerotic changes in coronary vessels. Diet and treatment with 3-hydroxi-3-metilglutaril coenzyme A (HMG-CoA) reductase inhibitors helps to reduce low density lipoprotein cholesterol (LDL-Ch) blood concentration up to recommended level of 3.0 mmol/l in most patients but in some patients particularly with familial dyslipidemias cholesterol concentration remains increased even after treatment with maximal doses of lipid-regulating agents or their combinations. The most frequently used mechanical methods of cholesterol removal from blood include the procedures of extracorporeal apheresis. Low density lipoprotein (LDL) apheresis not only significantly reduces the blood concentrations of total cholesterol (TCh), and LDL-Ch, lipoprotein (a) (Lp(a) and fibrinogen but also stops the progression of atherosclerosis in coronary vessels.
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PMID:[Low density lipoprotein apheresis]. 1470 3

Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin. Hence, the aim of this study was to analyze the association between the SLCO1B1 c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G polymorphisms and lipid-lowering effect and safety of atorvastatin. A hundred and fifty six patients with hyperlipidemia IIa and IIb, all of Macedonian origin, were included in the study receiving atorvastatin 20 - 80 mg/day for 3 months. SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped using the TaqMan allelic discrimination assay. As parameters of atorvastatin response, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A (ApoAI), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), creatine phosphokinase (CPK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, using standard laboratory methods, at baseline and after 3 months of treatment. No statistically significant association between the different SLCO1B1 SNPs and atorvastatin response was observed. However, the carriers of c.521CC manifested a lower decrease in plasma levels of TG, TC, LDL-C and Lp(a), with percentage difference being 16%, 7%, 29% and 149%, respectively, compared to the carriers of c.521TT variant. Lower increase in HDL-C (271%) and ApoAI (293%) and higher increase in CPK (69%) in c.521CC carriers were also observed, confirming the lower OATP1B1 activity in carriers of the variant c.521 C allele. Similar results were obtained when a comparison between the percentage of biochemical parameter change was made between *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers. The lack of a statistically significant association between the SLCO1B1 polymorphism and atorvastatin response can be explained dominantly by the low number of individuals homozygous for the rare c.521C variant allele. Despite this limitation, the study offers valuable information on the influence of the genetic determinant SLCO1B1 on atorvastatin response in the Macedonian population.
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PMID:Influence of SLCO1B1 polymorphisms on atorvastatin efficacy and safety in Macedonian subjects. 2944 75


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