title: Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences.
abstract: The molecular basis of the processes that control two closely related traits, the absorption of cholesterol from the intestines and plasma plant sterol levels, are only partially understood. The discovery that mutations in two novel hemitransporters, ATP binding cassette transporter G5 (ABCG5) and ABCG8, underlie a rare inborn error in plant sterol metabolism, beta-sitosterolemia, represents a major breakthrough in this field. More recently, genetic studies in the mouse that mapped loci in linkage with cholesterol absorption and plasma plant sterol levels and studies in humans that examined the relationship of plasma plant sterol levels to sequence variation in the ABCG5/ABCG8 locus suggested the involvement of other genes. Moreover, studies in beta-sitosterolemic patients, in ABCG5/ABCG8-targeted animals, and on a newly developed cholesterol absorption inhibitor, ezetimibe, suggest commonalities and differences in the regulation of the two traits. This review summarizes the evidence for genetic control of cholesterol absorption and plasma plant sterol levels, presents the evidence for commonalities and differences between the two traits, and discusses recent developments and future perspectives in this field.
authors.affiliation: Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. sehayee@rockefeller.edu
authors.forename: Ephraim
authors.initials: E
authors.lastname: Sehayek
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000042:Absorption; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D010840:Phytosterols / Q000097:blood*
chemical_list: D018528:ATP-Binding Cassette Transporters; D010840:Phytosterols; D002784:Cholesterol