Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0154251 (lipid disorder)
 795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test whether abnormalities in multiphasic release of lipoprotein lipase are associated with hypertriglyceridemia in diabetes mellitus, postheparin lipolytic activity (PHLA) was measured during a high-dose, constant heparin infusion in 20 diabetic subjects with hypertriglyceridemia, 25 nondiabetic hypertriglyceridemic subjects and 7 normal subjects. The standard low heparin dose PHLA and the PHLa during the early phase of the heparin infusion were the same in all groups. In constrast, the PHLA during the late phase of the heparin infusion was lower in the 12 untreated diabetic subjects than in the 25 nondiabetic hypertriglyceridemic and the 7 normal subjects (p less than 0.001). An abnormality in late phase PHLA in the untreated diabetic subjects was more apparent when it was compared to the level of PHLA attained during the early phase of the heparin infusion (Equilibrium PHLA/60 min PHLA). The relative PHLA in the late phase of the infusion was lower in the untreated diabetic subjects (0.671 +/- 0.147) than in the nondiabetic hypertriglyceridemic subjects (0.847 +/- 0.019, p less than 0.001), or in the chronically treated diabetic subjects (0.823 +/- 0.108, p less than 0.05). Among the untreated diabetic subjects, increasing fasting glucose levels were associated with both decreasing absolute PHLA levels at the late phase of the infusion (r = 0.61, p less than 0.02) and greater decreases in relative PHLA during the infusion (r = -0.80, p less than 0.001). Treatment of the diabetes with long-term oral sulfonylurea or insulin therapy corrected the abnormality in the late phase PHLA with an associated decrease in plasma triglyceride levels (p less than 0.001). In five subjects with a deficient PHLA response to a standard, low dose of heparin, the PHLA response was low throughout the heparin infusion. With treatment, the PHLA response to the low heparin dose corrected rapidly toward normal in those two diabetic subjects with PHLa deficiency, and the early PHLA response during the heparin infusion increased. However, the late phase abnormality in all untreated diabetic subjects did not correct to normal until after several months of antihyperglycemic therapy. In the untreated diabetic subjects the degree of elevation of the plasma triglyceride level appeared to result from the interaction of the abnormality in PHLA with the presence or absence of an inherited familial lipid disorder.
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PMID:Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes). 116 28

Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in a subset of patients presenting with this lipid disorder, the biochemical and genetic defects that lead to hypertriglyceridaemia have been well characterized. These individuals present with the familial chylomicronaemia syndrome, a rare genetic disorder that is inherited as an autosomal recessive trait, and is characterized by severe fasting hypertriglyceridaemia, massive accumulations of chylomicrons in plasma, and recurrent bouts of pancreatitis. The two major causes of the familial chylomicronaemia syndrome are a deficiency of the enzyme, lipoprotein lipase (LPL), or its cofactor, apolipoprotein (apo) C-II. Together, these two proteins initiate the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins. In the past decade our understanding of the underlying molecular defects that lead to familial chylomicronaemia has been greatly enhanced by the identification of mutations in the genes for LPL and apoC-II. Characterization of these defects has provided new insights into the structure and function of apoC-II and LPL and established the important role that these two proteins play in normal triglyceride metabolism.
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PMID:Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. 161 90

The fibric acid derivatives, including fenofibrate, significantly reduce very low-density lipoprotein triglyceride concentrations by stimulating lipoprotein lipase activity, thereby increasing very low-density lipoprotein catabolism. These agents may also reduce the hepatic secretion of nascent very low-density lipoprotein, but this effect is less consistent. Effects on low-density lipoprotein metabolism appear to depend upon the lipid disorder present before therapy. If hypertriglyceridemia and normal or low low-density lipoprotein levels are present, fibrate therapy is associated with a rise in low-density lipoprotein levels. This is due to a decreased fractional catabolism of low-density lipoprotein from an unusually high clearance to a more normal value. Treating pre-existing hypercholesterolemia usually results in a significant decrease in low-density lipoprotein levels. In this disorder, there is a demonstrable increase in low-density lipoprotein receptor-mediated clearance. It is not known at which site these drugs act to increase low-density lipoprotein receptor function in the latter patients. Some studies suggest that fibrate therapy increases high-density lipoprotein apolipoprotein AI production, but how this occurs has not been defined.
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PMID:Changes in lipoprotein kinetics during therapy with fenofibrate and other fibric acid derivatives. 331 56

The effects of treatment on plasma total triglyceride, total cholesterol, and plasma postheparin lipase activities have not been evaluated in non-insulin-dependent diabetic (NIDD) subjects without a coexisting familial lipid disorder. In 49 untreated NIDD subjects, there was a linear relationship between glycosylated hemoglobin (GHb) and triglyceride (r = 0.35, P less than 0.02). This correlation was improved after adjusting for the effects of obesity by a partial correlation analysis. After therapy, there was a significant relationship between the change in GHb and the change in triglyceride. To determine whether changes in lipid removal from plasma may contribute to the decrease in plasma lipid concentrations during treatment, the plasma postheparin lipoprotein lipase and hepatic lipase activities were evaluated in a subgroup (N = 8) of these NIDD subjects before and after 1 and 3 mo of therapy. Plasma postheparin hepatic lipase activity in the NIDD subjects was not different from that observed in six normal control subjects and did not change during therapy. In contrast, plasma postheparin lipoprotein lipase activity was lower in the untreated NIDD subjects than in the control subjects. Analysis of the two phases (early and late) of the postheparin lipoprotein lipase activity in plasma showed that the abnormal early phase in untreated NIDD corrected to normal values in less than a month, but the late phase was not corrected until the 3-mo measurement. These findings suggest that some NIDD subjects have a defect in heparin releasable lipoprotein lipase activity, which is reversed with improved glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response of plasma triglyceride, cholesterol, and lipoprotein lipase to treatment in non-insulin-dependent diabetic subjects without familial hypertriglyceridemia. 635 82

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by an increase in cholesterol and/or triglyceride levels in multiple individuals of the same family. Prior reports document a decreased activity of lipoprotein lipase (LPL) in FCHL, and studies of the role of LPL in the remodeling of nascent lipoproteins suggest that disturbances in LPL function could underlie FCHL. We studied the LPL gene in 31 unrelated individuals with FCHL. A total of 25 DNA changes (13 "silent" substitutions and 12 DNA changes resulting in amino acid substitutions) were detected in 16 patients. Three new exonic polymorphisms as well as a previously described Ser447-->stop and an Asp9-->Asn substitution were seen with similar frequency on control and FCHL chromosomes. Two novel DNA changes resulting in an Asp21-->Val and an His44-->Tyr substitution were seen in only two FCHL individuals. In vitro studies showed no effect of these mutations on LPL catalytic activity. LPL mutations impairing catalytic activity did not represent a significant factor leading to FCHL in this population. Variations in any portion of the coding region of the LPL gene affecting other functions besides catalysis are not a frequent cause of FCHL.
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PMID:Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia. 804 85

Familial hypercholesterolemia is a disorder of lipid metabolism associated with a highly increased risk for cardiovascular disease. Since in such patients even combined drug therapy often fails to decrease low-density lipoprotein (LDL) cholesterol levels sufficiently, extracorporeal LDL elimination has been developed. We treated eight adult patients with LDL immunoadsorption using antibodies against apolipoprotein B without additional lipid-lowering drug therapy for 3 years; this procedure was performed at weekly intervals. By one treatment session, LDL cholesterol and lipoprotein(a) levels were decreased by 55%. Under regular treatment, mean LDL cholesterol levels of 165 mg/dL between two consecutive treatment sessions could be reached, compared with 522 +/- 24 mg/dL before any treatment. As high-density lipoprotein (HDL) cholesterol levels increased under regular treatment, the LDL/HDL cholesterol ratio decreased from 13.4 to 3.4. Positive influences on plasma and whole-blood viscosity as well as on erythrocyte aggregation also seem to be beneficial with regard to retarding atherosclerosis. Very-low-density lipoprotein (VLDL) levels were reduced by approximately 50% after treatment, accompanied by a marked increase of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity. The effects of LDL apheresis on hemostasis, complement activation transport proteins, and hematological parameters were found to be small. In addition, no side effects amounting to any major clinical relevance occurred in any of the patients. After 3 years of LDL apheresis, a decrease in the frequency of anginal chest pain and ST segment depression on exercise testing and a marked reduction of tendon xanthoma size were observed.
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PMID:Three-year treatment of familial heterozygous hypercholesterolemia by extracorporeal low-density lipoprotein immunoadsorption with polyclonal apolipoprotein B antibodies. 834 99

Hypertriglyceridemia is a heterogeneous lipid disorder often running in families. Variation in the apolipoprotein B (apo B) gene has been associated with serum triglyceride levels. Recently, a role of the amino-terminal end of apo B in binding with lipoprotein lipase (LPL) has been suggested. We screened the 5' end of the apo B gene in 76 Finnish severely hypertriglyceridemic (> 6 mmol/l) patients, using a single-strand conformation polymorphism (SSCP) screening method. We detected a previously unreported polymorphic C2316-->A change, causing a Val703-->Ile substitution. The minor 703 Ile allele frequency was 0.04 in hypercholesterolemic and normolipidemic population samples. This allele was associated with lower serum triglyceride levels in a normolipidemic population sample. Analysis of two previously reported polymorphisms also located in the amino-terminal domain of apo B (Thr71-->Ile and Val591-->Ala) revealed elevating effects on serum apo B concentrations in hypertriglyceridemic individuals. The 591 Ala allele was associated with elevated apo B (P=0.011), and individuals with both minor alleles (apo B 591 Ala + and apo B 71 Ile +) had higher apo B levels compared to subjects homozygous for both common alleles (P=0.004). Although no DNA sequence change seemed to be the cause of hypertriglyceridemia in our patients, genetic variation in the 5' end of the apo B gene may contribute to changes in serum apo B levels in hypertriglyceridemic patients.
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PMID:Genetic variation in the amino-terminal part of apolipoprotein B: studies in hyperlipidemic patients. 969 Sep 21

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by elevated levels of plasma cholesterol and triglycerides that is present in 10% to 20% of patients with premature coronary artery disease. To study the pathophysiological basis and genetics of FCHL, we previously reported recruitment of 18 large families. We now report linkage studies of 14 candidate genes selected for their potential involvement in the aspects of lipid and lipoprotein metabolism that are altered in FCHL. We used highly polymorphic markers linked to the candidate genes, and these markers were analyzed using several complementary, nonparametric statistical allele-sharing linkage methodologies. This current sample has been extended over the one in which we identified an association with the apolipoprotein (apo) AI-CIII-AIV gene cluster. We observed evidence for linkage of this region and FCHL (P<0.001), providing additional support for its involvement in FCHL. We also identified a new locus showing significant evidence of linkage to the disorder: the lecithin:cholesterol acyltransferase (LCAT) locus (P<0.0006) on chromosome 16. In addition, analysis of the manganese superoxide dismutase locus on chromosome 6 revealed a suggestive linkage result in this sample (P<0.006). Quantitative traits related to FCHL also provided some evidence of linkage to these regions. No evidence of linkage to the lipoprotein lipase gene, the microsomal triglyceride transfer protein gene, or several other genes involved in lipid metabolism was observed. The data suggest that the lecithin:cholesterol acyltransferase and apolipoprotein AI-CIII-AIV loci may act as modifying genes contributing to the expression of FCHL.
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PMID:Linkage of a candidate gene locus to familial combined hyperlipidemia: lecithin:cholesterol acyltransferase on 16q. 1055 18

Type I hyperlipoproteinemia (type I HLP) is a rare disorder of lipid metabolism characterized by fasting chylomicronemia and reduced postheparin plasma lipoprotein lipase (LPL) activity. Most cases of type I HLP are due to genetic defects in the LPL gene or in its activator, the apolipoprotein CII gene. Several cases of acquired type I HLP have also been described in the course of autoimmune diseases due to the presence of circulating inhibitors of LPL. Here we report a case of type I HLP due to a transient defect of LPL activity during puberty associated with chronic idiopathic urticaria (CIU). The absence of any circulating LPL inhibitor in plasma during the disease was demonstrated. The LPL genotype showed that the patient was heterozygous for the D9N variant. This mutation, previously described, can explain only minor defects in the LPL activity. The presence of HLP just after the onset of CIU, and the elevation of the LPL activity with remission of the HLP when the patient recovered from CIU, indicate that type I HLP was caused by CIU. In summary, we report a new etiology for type I HLP - a transient decrease in LPL activity associated with CIU and with absence of circulating inhibitors. This is the first description of this association, which suggests a new mechanism for type I HLP.
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PMID:Acquired lipoprotein lipase deficiency associated with chronic urticaria. A new etiology for type I hyperlipoproteinemia. 1057 67

Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.
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PMID:Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats. 1083 Nov 67


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