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Ernst J Schaefer - One of the best experts on this subject based on the ideXlab platform.
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abstract 567 genetic and clinical heterogeneity of marked high density Lipoprotein Deficiency
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Eliana Polisecki, Margaret R Diffenderfer, Bela F Asztalos, Andrew S Geller, Taylor Sacco, Sotirios K Karathanasis, Robert A Hegele, Ernst J SchaeferAbstract:Aim: Our goal was to assess the population prevalence, genetics and clinical phenotypes of subjects with marked HDL Deficiency. Methods: 200 subjects (26% female, mean age 52 years) with serum HDL-...
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diagnosis and treatment of high density Lipoprotein Deficiency
Progress in Cardiovascular Diseases, 2016Co-Authors: Ernst J Schaefer, Pimjai Anthanont, Margaret R Diffenderfer, Eliana Polisecki, Bela F AsztalosAbstract:Low serum high density Lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked Deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apoLipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I Deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase Deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.
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a kindred with fish eye disease corneal opacities marked high density Lipoprotein Deficiency and statin therapy
Journal of Clinical Lipidology, 2014Co-Authors: Susan M Dimick, Bela F Asztalos, Brigitte Sallee, Haydn P Pritchard, Jiri Frohlich, Ernst J SchaeferAbstract:Abstract A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density Lipoprotein (HDL) cholesterol (C), apoLipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable Lipoprotein-X, and had mean low-density Lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated. Their mean lecithin cholesterol acyltransferase (LCAT) activities, cholesterol esterification rates, and free cholesterol levels were 8%, 42%, and 258% of normal, whereas their parents and 1 sibling had values that were 55%, 49%, and 114% of normal. The defect was due to 1 common variant in the LCAT gene in exon 1: c101t causing a proline34leucine substitution and a novel mutation c1177t causing a threonine37methionine substitution, with the former variant being found in the father and 1 sibling, and the latter mutation being found in the mother, and both mutations being present in the 2 probands. FED is distinguished from familial LCAT Deficiency (FLD) by the lack of anemia, splenomegaly, and renal insufficiency as well as normal or increased LDL-C. Both FLD and FED cases have marked HDL Deficiency and corneal opacification, and FED cases may have premature coronary heart disease in contrast to FLD cases. Therapy, using presently available agents, in FED should be to optimize LDL-C levels, and 1 proband responded well to statin therapy. The investigational use of human recombinant LCAT as an enzyme source is ongoing.
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clinical presentation laboratory values and coronary heart disease risk in marked high density Lipoprotein Deficiency states
Journal of Clinical Lipidology, 2008Co-Authors: Raul D Santos, Eliana Polisecki, Bela F Asztalos, L Martinez, Marcio H Miname, Ernst J SchaeferAbstract:Abstract Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density Lipoprotein (HDL) Deficiency (HDL cholesterol levels
Bela F Asztalos - One of the best experts on this subject based on the ideXlab platform.
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abstract 567 genetic and clinical heterogeneity of marked high density Lipoprotein Deficiency
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Eliana Polisecki, Margaret R Diffenderfer, Bela F Asztalos, Andrew S Geller, Taylor Sacco, Sotirios K Karathanasis, Robert A Hegele, Ernst J SchaeferAbstract:Aim: Our goal was to assess the population prevalence, genetics and clinical phenotypes of subjects with marked HDL Deficiency. Methods: 200 subjects (26% female, mean age 52 years) with serum HDL-...
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diagnosis and treatment of high density Lipoprotein Deficiency
Progress in Cardiovascular Diseases, 2016Co-Authors: Ernst J Schaefer, Pimjai Anthanont, Margaret R Diffenderfer, Eliana Polisecki, Bela F AsztalosAbstract:Low serum high density Lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked Deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apoLipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I Deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase Deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.
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a kindred with fish eye disease corneal opacities marked high density Lipoprotein Deficiency and statin therapy
Journal of Clinical Lipidology, 2014Co-Authors: Susan M Dimick, Bela F Asztalos, Brigitte Sallee, Haydn P Pritchard, Jiri Frohlich, Ernst J SchaeferAbstract:Abstract A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density Lipoprotein (HDL) cholesterol (C), apoLipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable Lipoprotein-X, and had mean low-density Lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated. Their mean lecithin cholesterol acyltransferase (LCAT) activities, cholesterol esterification rates, and free cholesterol levels were 8%, 42%, and 258% of normal, whereas their parents and 1 sibling had values that were 55%, 49%, and 114% of normal. The defect was due to 1 common variant in the LCAT gene in exon 1: c101t causing a proline34leucine substitution and a novel mutation c1177t causing a threonine37methionine substitution, with the former variant being found in the father and 1 sibling, and the latter mutation being found in the mother, and both mutations being present in the 2 probands. FED is distinguished from familial LCAT Deficiency (FLD) by the lack of anemia, splenomegaly, and renal insufficiency as well as normal or increased LDL-C. Both FLD and FED cases have marked HDL Deficiency and corneal opacification, and FED cases may have premature coronary heart disease in contrast to FLD cases. Therapy, using presently available agents, in FED should be to optimize LDL-C levels, and 1 proband responded well to statin therapy. The investigational use of human recombinant LCAT as an enzyme source is ongoing.
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marked high density Lipoprotein Deficiency due to apoLipoprotein a i tomioka codon 138 deletion
Atherosclerosis, 2009Co-Authors: Masamichi Wada, Bela F Asztalos, Tatsuya Iso, Noriaki Takama, Tadashi Nakajima, Yukihiro Seta, Katsumi Kaneko, Yasuhiro Taniguchi, Hideo Kobayashi, Katsuyuki NakajimaAbstract:Abstract We report a novel apoLipoprotein A-I (apoA-I) mutation identified in a 64-year-old patient with marked plasma high density Lipoprotein (HDL) cholesterol (4 mg/dl) and apoA-I (5 mg/dl) Deficiency, prior myocardial infarction, and moderate corneal opacities. Coronary angiography revealed extensive atherosclerosis in all three major vessels. Genomic DNA sequencing of the proband revealed a homozygous novel deletion of two successive adenine residues in codon 138 in the apoA-I gene, resulting in a frameshift mutation at amino acid residues 138–178, which we have designated as apoA-I Tomioka. His elder brother was also homozygous for apoA-I Tomioka with marked HDL cholesterol and apoA-I Deficiency, but had no clinical evidence of coronary heart disease. Other family members including three siblings and two sons were heterozygous for the mutation, and had approximately 50% of normal plasma HDL cholesterol, and apoA-I. Analysis of apoA-I-containing HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I HDL particles in the homozygotes, while in heterozygotes, the mean concentrations of apoA-I in large α-1 and very small preβ-1 HDL subpopulations were significantly decreased at about 35% of normal. Thus, apoA-I Tomioka, a novel deletion mutation in codon 138 of the apoA-I gene, is the causative defect in this case of HDL Deficiency.
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clinical presentation laboratory values and coronary heart disease risk in marked high density Lipoprotein Deficiency states
Journal of Clinical Lipidology, 2008Co-Authors: Raul D Santos, Eliana Polisecki, Bela F Asztalos, L Martinez, Marcio H Miname, Ernst J SchaeferAbstract:Abstract Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density Lipoprotein (HDL) Deficiency (HDL cholesterol levels
Laura Calabresi - One of the best experts on this subject based on the ideXlab platform.
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severe high density Lipoprotein Deficiency associated with autoantibodies against lecithin cholesterol acyltransferase in non hodgkin lymphoma
JAMA Internal Medicine, 2012Co-Authors: Sara Simonelli, Cesare R Sirtori, Elisabetta Gianazza, Giuliana Mombelli, Alighiero Bondioli, Giovanni Ferraro, Silvana Penco, Guido Franceschini, Laura CalabresiAbstract:An antibody against the lecithin:cholesterol acyltransferase (LCAT) enzyme, which negates cholesterol esterification in plasma, causing severe high-density Lipoprotein Deficiency (HD), was identified in a woman with a large-cell non-Hodgkin lymphoma. Successful treatment of the lymphoma resulted in clearance of the antibody and complete correction of the defective cholesterol esterification and HD. To our knowledge, an acquired LCAT Deficiency leading to severe HD has not been reported previously in association with a malignant disease, and this patient represents the first such documented case.
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functional lecithin cholesterol acyltransferase is not required for efficient atheroprotection in humans
Circulation, 2009Co-Authors: Laura Calabresi, Cesare R Sirtori, D Baldassarre, Samuela Castelnuovo, Paola Conca, L Bocchi, C Candini, B Frigerio, M Amato, Paola AlessandriniAbstract:Background— Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) Deficiency, a very rare metabolic disorder with 2 hypoalphaLipoproteinemia syndromes: classic familial LCAT Deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphaLipoproteinemia cases with LCAT Deficiency should be at increased cardiovascular risk because of high-density Lipoprotein Deficiency and defective reverse cholesterol transport. Methods and Results— The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls (P=0.0003 and P=0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype...
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Functional Lecithin: Cholesterol Acyltransferase Is Not Required for Efficient Atheroprotection in Humans
'Ovid Technologies (Wolters Kluwer Health)', 2009Co-Authors: Laura Calabresi, D Baldassarre, Samuela Castelnuovo, Paola Conca, L Bocchi, C Candini, B Frigerio, M Amato, Paola AlessandriniAbstract:BACKGROUND: Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) Deficiency, a very rare metabolic disorder with 2 hypoalphaLipoproteinemia syndromes: classic familial LCAT Deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphaLipoproteinemia cases with LCAT Deficiency should be at increased cardiovascular risk because of high-density Lipoprotein Deficiency and defective reverse cholesterol transport. METHODS AND RESULTS: The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls (P=0.0003 and P=0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose-dependent effect in reducing carotid IMT (P=0.0003 for average IMT; P=0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT Deficiency (ie, familial LCAT Deficiency or fish-eye disease). CONCLUSIONS: Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density Lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk
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modulated serum activities and concentrations of paraoxonase in high density Lipoprotein Deficiency states
Atherosclerosis, 1998Co-Authors: Richard W James, Laura Calabresi, Arnold Von Eckardstein, G Assmann, Marieclaude Blatter Garin, Roberto Miccoli, Marju Tillykiesi, Marjariitta Taskinen, Guido FranceschiniAbstract:Paraoxonase is a high density Lipoprotein (HDL) associated enzyme with a hypothesised role in the protection of low density Lipoproteins (LDL) from oxidative stress. The present study examined paraoxonase in several genetically distinct HDL Deficiency states. Despite reduction or even absence of detectable HDL, enzyme activity was present in sera from A-I-Pisa, A-I-Helsinki, A-I-Milano and Tangier patients. Both enzyme activities and peptide concentrations were modulated (reduced) but specific activities were broadly similar to controls, suggesting an impact on peptide concentration rather than an inhibition of enzyme activity. Despite the absence of HDL in A-I-Pisa and Tangier subjects, there was no association of paraoxonase with very low density Lipoproteins or LDL. Paraoxonase function is maintained in HDL deficient states. It implies that certain HDL-associated anti-atherogenic processes may not be entirely compromised by HDL Deficiency. This has important implications for the cardiovascular risk associated with modulated HDL concentrations.
Eliana Polisecki - One of the best experts on this subject based on the ideXlab platform.
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abstract 567 genetic and clinical heterogeneity of marked high density Lipoprotein Deficiency
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Eliana Polisecki, Margaret R Diffenderfer, Bela F Asztalos, Andrew S Geller, Taylor Sacco, Sotirios K Karathanasis, Robert A Hegele, Ernst J SchaeferAbstract:Aim: Our goal was to assess the population prevalence, genetics and clinical phenotypes of subjects with marked HDL Deficiency. Methods: 200 subjects (26% female, mean age 52 years) with serum HDL-...
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diagnosis and treatment of high density Lipoprotein Deficiency
Progress in Cardiovascular Diseases, 2016Co-Authors: Ernst J Schaefer, Pimjai Anthanont, Margaret R Diffenderfer, Eliana Polisecki, Bela F AsztalosAbstract:Low serum high density Lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked Deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apoLipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I Deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase Deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.
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clinical presentation laboratory values and coronary heart disease risk in marked high density Lipoprotein Deficiency states
Journal of Clinical Lipidology, 2008Co-Authors: Raul D Santos, Eliana Polisecki, Bela F Asztalos, L Martinez, Marcio H Miname, Ernst J SchaeferAbstract:Abstract Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density Lipoprotein (HDL) Deficiency (HDL cholesterol levels
Mitsunobu Kawamura - One of the best experts on this subject based on the ideXlab platform.
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novel mutations in abca1 gene in japanese patients with tangier disease and familial high density Lipoprotein Deficiency with coronary heart disease
Biochimica et Biophysica Acta, 2001Co-Authors: Wei Huang, Kengo Moriyama, Takafumi Koga, Han Hua, Masato Ageta, Seiro Kawabata, Koji Mawatari, Takuro Imamura, Tanenao Eto, Mitsunobu KawamuraAbstract:Mutations in the ATP-binding cassette transporter 1 (ABCA1) gene have been recently identified as the molecular defect in Tangier disease (TD) and familial high density Lipoprotein Deficiency (FHA). We here report novel mutations in the ABCA1 gene in two sisters from a Japanese family with TD who have been described previously (S. Ohtaki, H. Nakagawa, N. Kida, H. Nakamura, K. Tsuda, S. Yokoyama, T. Yamamura, S. Tajima, A. Yamamoto, Atherosclerosis 49 (1983)) and a family with FHA. Both probands of TD and FHA developed coronary heart disease. Sequence analysis of the ABCA1 gene from the patients with TD revealed a homozygous G to A transition at nucleotide 3805 of the cDNA resulting in the substitution of Asp 1229 with Asn in exon 27, and a C to T at nucleotide 6181 resulting in the substitution of Arg 2021 with Trp in exon 47. Sequence analysis of the ABCA1 gene from the FHA patient revealed a homozygous 4 bp CGCC deletion from nucleotide 3787 to 3790 resulting in premature termination by frameshift at codon 1224. These mutations were confirmed by restriction digestion analysis, and were not found in 141 control subjects. Our findings indicate that mutations in the ABCA1 gene are associated with TD as well as FHA.