134 results match your criteria High HDL Cholesterol Hyperalphalipoproteinemia

Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population.

JAMA Cardiol 2022 01;7(1):55-64

Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Importance: The balance between the potential long-term clinical benefits and harms associated with genetic cholesteryl ester transfer protein (CETP) deficiency, mimicking pharmacologic CETP inhibition, is unknown.

Objective: To assess the relative benefits and harms associated with genetic CETP deficiency.

Design, Setting, And Participants: This study examined 2 similar prospective cohorts of the Danish general population, with data on a total of 102 607 participants collected from October 10, 1991, through December 7, 2018. Read More

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January 2022

ANGPTL3 and ANGPTL8 in Thai subjects with hyperalphalipoproteinemia and severe hypertriglyceridemia.

J Clin Lipidol 2021 Sep-Oct;15(5):752-759. Epub 2021 Sep 1.

Division of Endocrinology and Metabolism, Department of Medicine, and Hormonal and Metabolic Disorders Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Medicine, and Excellence Center for Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Electronic address:

Background: The role of ANGPTL3 and ANGPTL8 in lipid regulation in patients with very high levels of HDL-cholesterol and triglyceride is unknown.

Objective: We examined plasma levels of ANGPTL3 and ANGPTL8 in subjects with hyperalphalipoproteinemia (HALP) and in those with severe hypertriglyceridemia (HTG).

Methods: Plasma ANGPTL3 and ANGPTL8 levels were measured by ELISA in 320 subjects, consisting of HALP subjects with HDL-cholesterol ≥100 mg/dl (n=90) and healthy controls (n=90) and subjects with triglyceride ≥886 mg/dl (n=89) and control subjects (n=51). Read More

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Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases.

Life (Basel) 2021 Jun 18;11(6). Epub 2021 Jun 18.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties-University of Palermo, Via del Vespro, 129, 90127 Palermo, Italy.

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). Read More

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Atherosclerotic cardiovascular disease in hyperalphalipoproteinemia due to LIPG variants.

J Clin Lipidol 2021 Jan-Feb;15(1):142-150.e2. Epub 2020 Dec 24.

Division of Chemical Pathology, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory, 7925, Cape Town, South Africa. Electronic address:

Background: High density lipoprotein cholesterol (HDL-C) concentration correlates inversely with atherosclerotic cardiovascular disease (ASCVD) risk and is included in risk calculations. Endothelial lipase (EL) is a phospholipase that remodels HDL. Deficiency of EL due to mutations in its gene, LIPG, is associated with hyperalphalipoproteinemia. Read More

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November 2021

HDL cholesterol is associated with PBMC expression of genes involved in HDL metabolism and atherogenesis.

J Med Biochem 2020 Sep;39(3):372-383

National Research Centre for Preventive Medicine, Laboratory of Structural Fundamentals of Lipoprotein Metabolism, Moscow, Russia.

Background: To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis.

Methods: Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database. Read More

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September 2020

Development and Clinical Application of an Enzyme-Linked Immunosorbent Assay for Oxidized High-Density Lipoprotein.

J Atheroscler Thromb 2021 Jul 17;28(7):703-715. Epub 2020 Oct 17.

Department of Cardiology, Rinku General Medical Center.

Aims: HDL particles have various anti-atherogenic functions, whereas HDL from atherosclerotic patients was demonstrated to be dysfunctional. One possible mechanism for the formation of dysfunctional HDL is the oxidation of its components. However, oxidized HDLs (Ox-HDLs) remain to be well investigated due to lack of reliable assay systems. Read More

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Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 03 19;1865(3):158592. Epub 2019 Dec 19.

Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Zuid-Holland, the Netherlands. Electronic address:

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. Read More

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Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis.

Ann Hepatol 2019 Nov - Dec;18(6):879-882. Epub 2019 Aug 22.

Department of Endocrinology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.

Introduction And Objectives: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC.

Patients: All patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. Read More

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September 2020

Paradoxical Hypercholesterolemia in an Otherwise Healthy Adult Man.

Lab Med 2020 Mar;51(2):217-220

Centre for Applied Science, Belfast Metropolitan College, Belfast, Northern Ireland.

Hypercholesterolemia is characterized by serum cholesterol levels greater than 5 mmol per L. However, the distribution of cholesterol among lipoprotein classes has a significant bearing on diagnosis: high-low-density lipoprotein (LDL) cholesterol suggests familial hypercholesterolemia, whereas high-high-density lipoprotein (HDL) cholesterol is associated with hyperalphalipoproteinemia. On routine screening, a 23-year-old man presented with a total cholesterol level of 7. Read More

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Paraoxonase-1 activities in individuals with different HDL circulating levels: Implication in reverse cholesterol transport and early vascular damage.

Atherosclerosis 2019 06 11;285:64-70. Epub 2019 Apr 11.

Department of Medical Sciences, Internal Medicine and CardioRespiratory Section, University of Ferrara, Ferrara, Italy. Electronic address:

Background And Aims: Epidemiological data showing that high-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular disease have led to the idea that cholesterol contained in this lipoprotein may be protective. Against, recent evidence suggests that the athero-protection from HDLs may result from other functions, unrelated to the carried cholesterol. HDL accessory proteins, such as paraoxonase 1 (PON1), have been suggested to endows HDL with antioxidant and anti-inflammatory properties and to contribute to the athero-protective function of the lipoprotein. Read More

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Shotgun proteomic analysis reveals proteome alterations in HDL of patients with cholesteryl ester transfer protein deficiency.

J Clin Lipidol 2019 Mar - Apr;13(2):317-325. Epub 2019 Jan 11.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Community Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Cardiology, Rinku General Medical Center, Osaka, Japan. Electronic address:

Background: We previously reported that the patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) show marked changes in the size and lipid compositions of high-density lipoprotein (HDL) and that they are not protected from atherosclerotic cardiovascular diseases, despite increased serum HDL-cholesterol (HDL-C) levels. HDL particles carry a variety of proteins, some of which are known to have antiatherogenic functions.

Objective: This study aimed to investigate the protein composition of HDL particles in patients with CETP-D. Read More

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The biochemical and genetic diagnosis of lipid disorders.

Curr Opin Lipidol 2019 04;30(2):56-62

Eurofins Genomics, Louisville, Kentucky, USA.

Purpose Of Review: To examine recent advances in our knowledge on the diagnosis of lipid disorders.

Recent Findings: Fasting values above the 99th percentile for direct LDL-cholesterol (LDL-C), lipoprotein(a), and triglycerides are greater than 225 mg/dl, greater than 160 mg/dl, and greater than 500 mg/dl (>5.82, >394, and >5. Read More

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Relation of High-Density Lipoprotein Charge Heterogeneity, Cholesterol Efflux Capacity, and the Expression of High-Density Lipoprotein-Related Genes in Mononuclear Cells to the HDL-Cholesterol Level.

Lipids 2018 10 15;53(10):979-991. Epub 2018 Nov 15.

Institute of Molecular Genetics of the Russian Academy of Sciences, 2, Kurchatov Square, 123182, Moscow, Russia.

The heterogeneity and content of human plasma high-density lipoprotein (HDL) related to their atheroprotective properties determined by various molecular and cellular mechanisms still remain to be completely clarified. For 29 atherosclerosis-free male subjects, we studied the relationship of plasma lipid levels and the content of apolipoprotein A-I (apoA-I)-containing HDL with preβ-electrophoretic mobility, the efficiency of BODIPY-cholesterol efflux from RAW 264.7 macrophages to apolipoprotein B (apoB)-deficient plasma, and the expression level of 22 genes related to HDL metabolism in mononuclear cells. Read More

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October 2018

Particle number analysis of lipoprotein subclasses by gel permeation HPLC in patients with cholesteryl ester transfer protein deficiency.

PLoS One 2018 5;13(1):e0190875. Epub 2018 Jan 5.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Objective: We previously reported that patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) have a higher prevalence of atherosclerotic cardiovascular disease, in spite of increased HDL-C levels. However, characterization of HDL in CETP-D has not been well described. Therefore, we examined HDL particle number (PN) rather than HDL-C level. Read More

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February 2018

Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection.

J Clin Lipidol 2018 Jan - Feb;12(1):110-115. Epub 2017 Nov 21.

Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine and the Veterans Affairs Medical Center, Baltimore, MD, USA. Electronic address:

Background: Hyperalphalipoproteinemia (HALP) is inversely correlated with coronary heart disease (CHD) although genetic variants associated with high serum levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be cardioprotective.

Objective: The objective of the study was to uncover novel genetic variants associated with HALP and possibly with reduced risk of CHD.

Methods: Exome sequencing data, HDL-C, and triglyceride levels were analyzed in 1645 subjects. Read More

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Paradoxical coronary artery disease in humans with hyperalphalipoproteinemia is associated with distinct differences in the high-density lipoprotein phosphosphingolipidome.

J Clin Lipidol 2017 Sep - Oct;11(5):1192-1200.e3. Epub 2017 Jul 8.

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with risk of coronary artery disease (CAD) in epidemiologic studies. Despite this, the directionality of this relationship and the underlying biology behind it remain to be firmly established, especially at the extremes of HDL-C levels.

Objective: We investigated differences in the HDL phosphosphingolipidome in a rare population of subjects with premature CAD despite high HDL-C levels to gain insight into the association between the HDL lipidome and CAD disease status in this unusual phenotype. Read More

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Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

Arterioscler Thromb Vasc Biol 2017 06 20;37(6):1068-1075. Epub 2017 Apr 20.

From the Center for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine (J.Z., D.Y., J.L., J.X., Y.G., Y.F., T.Z., J.S., Y.K., M.G.-B., Y.E.C.), Department of Internal Medicine, Nephrology (A.V.M., S.P.), University of Michigan Medical Center, Ann Arbor; Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Japan (M.N., T.K., J.F.); Department of Pharmaceutical Sciences, Biointerfaces Institute, College of Pharmacy, University of Michigan (R.A., A.S.); and Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (L.L.).

Objective: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial.

Approach And Results: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. Read More

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Involvement of CETP (Cholesteryl Ester Transfer Protein) in the Shift of Sphingosine-1-Phosphate Among Lipoproteins and in the Modulation of its Functions.

Arterioscler Thromb Vasc Biol 2017 Mar 26;37(3):506-514. Epub 2017 Jan 26.

From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan (M.K., H.I., Y.Y.); Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan (M.H.); and Department of Metabolism, Diabetes and Nephrology, Aizu Medical Center, Fukushima Medical University, Japan (K.T.).

Objective: Sphingosine-1-phosphate (S1P) is a vasoprotective lipid mediator. About two thirds of plasma S1P rides on high-density lipoprotein (HDL), and several pleiotropic properties of HDL have been ascribed to S1P. In human subjects, CETP (cholesteryl ester transfer protein) greatly influences HDL quantities. Read More

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Extremely elevated HDL-cholesterol levels are not associated with increased carotid intima-media thickness: data from ELSA Brasil.

J Clin Lipidol 2016 Jul-Aug;10(4):898-904.e1. Epub 2016 Mar 21.

Centro de Pesquisa Clínica e Epidemiológica do Hospital Universitário, University of Sao Paulo Medical School, Sao Paulo, Brazil.

Background: There is evidence that extremely elevated high-density lipoprotein cholesterol (HDL-c), that is, hyperalphalipoproteinemia (HALP) may indicate dysfunctional HDL, conferring increased cardiovascular risk.

Objective: We studied carotid intima-media thickness (cIMT) a marker of subclinical vascular disease according to HDL-c distribution.

Methods: cIMT was studied in subjects with "normal" HDL-c levels (HDL-c 40-50 mg/dL for men; 50-60 mg/dL for women, mean 49. Read More

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October 2017

Limitations of a Cardiac Risk (QRISK2) Calculator in Patients with High Density Lipoprotein (HDL).

High Blood Press Cardiovasc Prev 2016 Mar 23;23(1):47-50. Epub 2016 Feb 23.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Introduction: There is existing debate as to the relationship between blood concentration of HDL (high density lipoprotein) and cardiovascular outcomes. Patients with hyperalphalipoproteinaemia (HALP) have high HDL levels and this can be attributed to a variety of factors.

Aim And Methods: This study aims for the first time to examine the HALP cohort and understand demographics, relationship with cardiovascular disease (CVD) risk and scoring with a cardiac risk calculator (QRISK 2 calculator). Read More

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Unique features of high-density lipoproteins in the Japanese: in population and in genetic factors.

Shinji Yokoyama

Nutrients 2015 Apr 2;7(4):2359-81. Epub 2015 Apr 2.

Nutritional Health Science Research Centre and Bioscience and Biotechnology, Chubu University, Kasugai 487-8501, Japan.

Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Read More

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Cholesteryl ester transfer protein (CETP) deficiency and CETP inhibitors.

Mol Cells 2014 Nov 6;37(11):777-84. Epub 2014 Nov 6.

Laboratory Science, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. Read More

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November 2014

Flow-mediated dilation, carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia.

Nutr Metab Cardiovasc Dis 2014 Jul 1;24(7):777-83. Epub 2014 Mar 1.

Department of Pharmacy, University of Parma, Parma, Italy.

Background And Aims: The relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate.

Methods And Results: Twenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30-65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint(®)), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Read More

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A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum.

Shinji Yokoyama

Biochim Biophys Acta 2014 Apr 3;1841(4):495-504. Epub 2014 Jan 3.

Nutritional Health Science Research Center, Chubu University, Matsumoto-cho 1200, Kasugai 487-8501, Japan. Electronic address:

Cholesteryl ester transfer protein (CETP)-deficiency manifests a unique plasma lipoprotein profile without other apparent symptoms. It is highly common in East Asia while rather rare anywhere else. A potential environmental screening factor(s) may therefore contribute to this eccentric distribution, such as its selective advantage against a regional illness, most likely an infectious disease, in relation to plasma lipoproteins. Read More

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Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects.

Cardiovasc Diabetol 2013 Nov 22;12:173. Epub 2013 Nov 22.

Lipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Hospital das Clinicas, Faculty of Medical Sciences, University of Sao Paulo, Av, Dr, Arnaldo, 455 - room 3305, Sao Paulo CEP 01246-00, Brazil.

Background: We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects.

Methods: We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-₁HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. Read More

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November 2013

Two novel mutations in apolipoprotein C3 underlie atheroprotective lipid profiles in families.

Clin Genet 2014 May 24;85(5):433-40. Epub 2013 Jun 24.

Department of Vascular Medicine.

Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c. Read More

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Functional characterization of novel variants in the CETP promoter and the LIPC gene in subjects with hyperalphalipoproteinemia.

Clin Chim Acta 2013 Feb 5;416:92-5. Epub 2012 Dec 5.

Hormonal and Metabolic Disorders Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Patumwan, Bangkok 10330, Thailand.

Background: Variants in the CETP and the LIPC genes, encoding cholesteryl ester transfer protein and hepatic lipase, respectively, are associated with high levels of HDL-cholesterol or hyperalphalipoproteinemia (HALP). Recently, we have identified three novel variants in the CETP promoter and two novel variants in LIPC in Thai subjects with HALP. In this study, we investigated the functions of these 5 variants in vitro. Read More

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February 2013

CD36-related protein in Schistosoma japonicum: candidate mediator of selective cholesteryl ester uptake from high-density lipoprotein for egg maturation.

FASEB J 2013 Mar 29;27(3):1236-44. Epub 2012 Nov 29.

Nutritional Health Science Research Centre and Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.

Familial cholesteryl ester transfer protein (CETP) deficiency is more common in some East Asian populations than elsewhere, suggesting the possibility of a selective advantage of this genetic defect against regional infectious diseases. Historically, infection with the Asian blood fluke Schistosoma japonicum has been endemic in these regions, including Japan. We previously reported that eggs of S. Read More

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Segregation of LIPG, CETP, and GALNT2 mutations in Caucasian families with extremely high HDL cholesterol.

PLoS One 2012 27;7(8):e37437. Epub 2012 Aug 27.

Xenon Pharmaceuticals Inc., Burnaby, Canada.

To date, few mutations are described to underlie highly-elevated HDLc levels in families. Here we sequenced the coding regions and adjacent sequence of the LIPG, CETP, and GALNT2 genes in 171 unrelated Dutch Caucasian probands with HDLc≥90th percentile and analyzed segregation of mutations with lipid phenotypes in family members. In these probands, mutations were most frequent in LIPG (12. Read More

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February 2013