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A more recent version of this article appeared on September 1, 2004

Papers In Press, published online ahead of print June 21, 2004
J. Lipid Res., doi:10.1194/jlr.M400006-JLR200
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Submitted on January 12, 2004
Revised on April 27, 2004
Accepted on June 3, 2004

Phytosterolemia on the Island of Kosrae: A founder effect for a novel ABCG8 mutation results in a high carrier rate and increased plasma plant sterol levels

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, and Jan L. Breslow

Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021

Corresponding Author: sehayee{at}rockefeller.edu

Screening of 932 adults on the Pacific island of Kosrae for plasma plant sterol levels disclosed 3 subjects, two of them asymptomatic, with exceptionally high plasma levels compatible with the diagnosis of phytosterolemia. Sequencing the ABCG5 and ABCG8 genes revealed a novel ABCG8 exon 2 mutation consisting of a base change followed by a single base deletion. This mutation 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 1090 Kosraens revealed 150 were carriers, a 13.8 % carrier rate. DNA sequencing of 67 carriers revealed the same mutation as in the probands. In carriers, the levels of plasma campesterol and sitosterol were 55% and 30% higher than in non-carriers, respectively. Moreover, compared to non-carriers, 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 AI 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 suggests that heterozygosity for a mutated ABCG8 allele results in a modest increase in dietary cholesterol absorption and decrease in cholesterol biosynthesis.


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E. Sehayek, Y. Y. Fung, H. J. Yu, J. Lembcke, U. Ceglarek, D. Teupser, J. Thiery, D. Lutjohann, K. von Bergmann, and J. L. Breslow
A complex plasma plant sterol locus on mouse chromosome 14 has at least two genes regulating intestinal sterol absorption
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[Abstract] [Full Text] [PDF]


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