Phytosterolemia on the island of Kosrae

Screening of 932 adults on the Pacific island of Kosrae for plasma plant sterol levels disclosed three subjects, two of them asymptomatic, with phytosterolemia. Sequencing the ATP binding cassette subfamily G member 8 (ABCG8) gene revealed a novel exon 2 mutation that causes a change in codon 24 fro...

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Main Authors:	Ephraim Sehayek, Hannah J. Yu, Klaus von Bergmann, Dieter Lutjohann, Markus Stoffel, Elizabeth M. Duncan, Laura Garcia-Naveda, Jacqueline Salit, Maude L. Blundell, Jeffrey M. Friedman, Jan L. Breslow
Format:	Article
Language:	English
Published:	Elsevier 2004-09-01
Series:	Journal of Lipid Research
Subjects:	ATP binding cassette subfamily G member 8 cholesterol absorption population genetics
Online Access:	http://www.sciencedirect.com/science/article/pii/S0022227520312761

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collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ephraim Sehayek Hannah J. Yu Klaus von Bergmann Dieter Lutjohann Markus Stoffel Elizabeth M. Duncan Laura Garcia-Naveda Jacqueline Salit Maude L. Blundell Jeffrey M. Friedman Jan L. Breslow
spellingShingle	Ephraim Sehayek Hannah J. Yu Klaus von Bergmann Dieter Lutjohann Markus Stoffel Elizabeth M. Duncan Laura Garcia-Naveda Jacqueline Salit Maude L. Blundell Jeffrey M. Friedman Jan L. Breslow Phytosterolemia on the island of Kosrae Journal of Lipid Research ATP binding cassette subfamily G member 8 cholesterol absorption population genetics
author_facet	Ephraim Sehayek Hannah J. Yu Klaus von Bergmann Dieter Lutjohann Markus Stoffel Elizabeth M. Duncan Laura Garcia-Naveda Jacqueline Salit Maude L. Blundell Jeffrey M. Friedman Jan L. Breslow
author_sort	Ephraim Sehayek
title	Phytosterolemia on the island of Kosrae
title_short	Phytosterolemia on the island of Kosrae
title_full	Phytosterolemia on the island of Kosrae
title_fullStr	Phytosterolemia on the island of Kosrae
title_full_unstemmed	Phytosterolemia on the island of Kosrae
title_sort	phytosterolemia on the island of kosrae
publisher	Elsevier
series	Journal of Lipid Research
issn	0022-2275
publishDate	2004-09-01
description	Screening of 932 adults on the Pacific island of Kosrae for plasma plant sterol levels disclosed three subjects, two of them asymptomatic, with phytosterolemia. Sequencing the ATP binding cassette subfamily G member 8 (ABCG8) gene revealed a novel exon 2 mutation that causes a change in codon 24 from glutamine to histidine and a frame shift followed by a premature stop codon, precluding the formation of a functional ABCG8 protein. Genotyping of 1,090 Kosraens revealed 150 as carriers, a 13.8% carrier rate. DNA sequencing of 67 carriers revealed the same mutation as in the probands. In carriers, plasma campesterol and sitosterol levels were 55% and 30% higher, respectively, than in noncarriers. Moreover, compared with noncarriers, carriers showed 21% lower plasma levels of lathosterol, a surrogate marker for cholesterol biosynthesis. There was no difference between the groups in plasma total cholesterol, triglycerides, apolipoprotein B, or apolipoprotein A-I levels.In summary, on the island of Kosrae, a strong founder effect of a mutant ABCG8 allele results in a large number of carriers with increased plasma plant sterol levels and decreased lathosterol levels. The latter finding suggests that heterozygosity for a mutated ABCG8 allele results in a modest increase in dietary cholesterol absorption and a decrease in cholesterol biosynthesis.
topic	ATP binding cassette subfamily G member 8 cholesterol absorption population genetics
url	http://www.sciencedirect.com/science/article/pii/S0022227520312761
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spelling	doaj-6bf4d195267f4d56a7a7f1b0c20490bd2021-04-27T04:39:32ZengElsevierJournal of Lipid Research0022-22752004-09-0145916081613Phytosterolemia on the island of KosraeEphraim Sehayek0Hannah J. Yu1Klaus von Bergmann2Dieter Lutjohann3Markus Stoffel4Elizabeth M. Duncan5Laura Garcia-Naveda6Jacqueline Salit7Maude L. Blundell8Jeffrey M. Friedman9Jan L. Breslow10Laboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyLaboratories of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY; Metabolic Diseases, The Rockefeller University, New York, NY; Molecular Genetics, The Rockefeller University, New York, NY; Department of Clinical Pharmacology, University of Bonn, Bonn, GermanyScreening of 932 adults on the Pacific island of Kosrae for plasma plant sterol levels disclosed three subjects, two of them asymptomatic, with phytosterolemia. Sequencing the ATP binding cassette subfamily G member 8 (ABCG8) gene revealed a novel exon 2 mutation that causes a change in codon 24 from glutamine to histidine and a frame shift followed by a premature stop codon, precluding the formation of a functional ABCG8 protein. Genotyping of 1,090 Kosraens revealed 150 as carriers, a 13.8% carrier rate. DNA sequencing of 67 carriers revealed the same mutation as in the probands. In carriers, plasma campesterol and sitosterol levels were 55% and 30% higher, respectively, than in noncarriers. Moreover, compared with noncarriers, carriers showed 21% lower plasma levels of lathosterol, a surrogate marker for cholesterol biosynthesis. There was no difference between the groups in plasma total cholesterol, triglycerides, apolipoprotein B, or apolipoprotein A-I levels.In summary, on the island of Kosrae, a strong founder effect of a mutant ABCG8 allele results in a large number of carriers with increased plasma plant sterol levels and decreased lathosterol levels. The latter finding suggests that heterozygosity for a mutated ABCG8 allele results in a modest increase in dietary cholesterol absorption and a decrease in cholesterol biosynthesis.http://www.sciencedirect.com/science/article/pii/S0022227520312761ATP binding cassette subfamily G member 8cholesterol absorptionpopulation genetics

Phytosterolemia on the island of Kosrae

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