Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistin, specifically secreted from adipocytes, antagonizes insulin and represents a promising candidate gene for type 2 diabetes. We reported that a frequent single nucleotide polymorphism (SNP) +299G>A in this gene is not associated with type 2 diabetes. To determine whether this SNP affects insulin resistance syndrome associated with type 2 diabetes, we examined its effects on susceptibility to obesity, hyperlipidemia and hypertension in type 2 diabetic subjects and on susceptibility to type 2 diabetes by interaction with other frequent genes involved in lipid metabolism, namely, beta3-adrenergic receptor (b3AR) Trp64Arg, phosphodiesterase 3B (PDE3B) c.1389G>A or lysosomal acid lipase (LAL) Thr-6Pro. The 99 type 2 diabetic and 99 control subjects were typed by PCR direct sequencing or PCR-RFLP. No differences in frequencies of obesity, hyperlipidemia and hypertension were found between the type 2 diabetic subjects with G/G and those with G/A or A/A genotypes of the resistin SNP. When the combination of the resistin SNP with each of b3AR, PDE3B and LAL SNPs was assessed, no association with type 2 diabetes was evident. Therefore, the frequent SNP +299G>A in the resistin gene is unlikely to have major effects on susceptibility to insulin resistance syndrome associated with type 2 diabetes in Japanese subjects.
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PMID:The absence of evidence for major effects of the frequent SNP +299G>A in the resistin gene on susceptibility to insulin resistance syndrome associated with Japanese type 2 diabetes. 1296 9

The association of elevated lipoprotein (a) (Lp(a)) with an increased risk for coronary events is clearly established. This increased risk may in part be due to the activation of monocytes as major cells involved in atherogenesis. High concentrations of plasma Lp(a) were shown to influence the gene expression of human blood monocytes and in the present study we demonstrate a reduced abundance of the lysosomal acid lipase (LAL) mRNA in monocytes of patients with coronary disease and selective Lp(a) hyperlipidemia. This is also supported by in vitro studies where purified Lp(a) but not low-density lipoprotein (LDL) was shown to downregulate mRNA levels of the LAL in control monocytes. A correlation of Lp(a) serum levels and the proinflammatory cytokine IL-6 was recently also described. Therefore, we investigated whether Lp(a) is capable to enhance the release of this acute phase cytokine from human blood monocytes. Purified Lp(a) led to an increased secretion of IL-6, but not TNF-alpha arguing against a general activation of these cells. The association of reduced LAL activity with the premature development of coronary artery disease has been demonstrated in patients with hypercholesterolemia, and in the present study we show for the first time that LAL expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a). In addition, increased levels of IL-6 also predict future cardiovascular events and IL-6 secretion was also induced by purified Lp(a).
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PMID:Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes. 1297 90

Cholesteryl ester storage disease (CESD) is an autosomal recessive disorder resulting from lysosomal acid lipase deficiency and is usually characterized by hepatomegaly and hyperlipidemia. This paper reports a two-year-old boy who had hepatosplenomegaly, hyperlipidemia and hypertransaminasemia determined incidentally. The liver biopsy sample was orange-yellow in appearance. Microscopically, microvesicular steatosis and birefringent crystals were seen in liver biopsy. The diagnosis of CESD was confirmed by the reduced human acid lipase activity in peripheral leukocytes. Simvastatin therapy was given and tolerated without side effects. Our patient is the youngest reported case in the literature treated with 3-hydroxy 3-methyl glutaryl (HMG) CoA reductase inhibitor.
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PMID:Cholesteryl ester storage disease in a young child presenting as isolated hepatomegaly treated with simvastatin. 1684 16

Cyclosporine A (CsA)-induced nephrotoxicity hampers the immense therapeutic potential of such a powerful immunosuppressant. The present study was conducted with an aim to explicate the contribution of sulphated polysaccharides (SPS) in abating the lipid abnormalities induced by CsA in the rat kidney. Hyperlipidemia associated with nephrotic syndrome may play a role in the worsening of renal function. Male albino Wistar rats sorted into four groups were used for the study. CsA was given at a dose of 25 mg/kg body weight, orally for 21 days. Significant alterations in the lipid profile as well an increase in the activity of cholesterol ester synthase, coupled with a decrease in cholesterol ester hydrolase and lipoprotein lipase enzyme activities were noted in the plasma and kidneys of CsA-administered rats. A marked increase in the lipoprotein fractions, low-density lipoprotein (LDL) and very low density lipoprotein (VLDL), along with a decrease in the HDL level were found in CsA-administered rats. The degree of nephrotoxicity allied with lipid discrepancies was evident from augmented urinary excretion of urea, uric acid and creatinine. Further, an enhanced susceptibility of the apo B-containing lipoproteins (LDL + VLDL) to oxidation in vitro, induced by copper ions was also found in the plasma of CsA given groups. While SPS co-treated groups (5 mg/kg body weight, subcutaneously) revealed a normalized lipid profile and lipid metabolizing enzymes, the supplementation of SPS also brought back the elevated urinary constituents close to that of the controls and substantially minimized the oxidative changes. With these observations, it may be concluded herein that SPS may be an ideal choice as a renoprotective and hypolipidemic agent against CsA-induced hyperlipidemic nephropathy.
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PMID:Protective role of sulphated polysaccharides in abating the hyperlipidemic nephropathy provoked by cyclosporine A. 1701 61

Cholesterol ester storage disease is a rare autosomal recessive storage disorder resulting from lysosomal acid lipase deficiency. Two siblings manifested with hepatosplenomegaly, ptosis, and bilateral external ophthalmoplegia. Evaluation revealed hyperlipidemia and bilateral adrenal calcifications. Leukocyte acid lipase levels were significantly low in both the patients, compared with controls, suggesting a diagnosis of cholesterol ester storage disease. Ptosis and external ophthalmoplegia have hitherto not been reported in cholesterol ester storage disease.
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PMID:Cholesterol ester storage disease with unusual neurological manifestations in two siblings: a report from South India. 1817 60

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.
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PMID:Orthotopic liver transplantation in an adult with cholesterol ester storage disease. 2343 May 18

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.
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PMID:Lysosomal acid lipase deficiency in all siblings of the same parents. 2850 15