Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences

Ephraim Sehayek

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

Corresponding Author: sehayee{at}rockefeller.edu

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, ABCG5 and ABCG8, underlie a rare inborn error in plant sterols metabolism, b-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 suggest the involvement of other genes. Moreover, studies in b-sitosterolemic patients, Abcg5/Abcg8 targeted animals and studies 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.

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