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Correspondence to:
Jonathan C. Cohen, at Center for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9052., jonathan.cohen{at}utsouthwestern.edu (E-mail)
The plasma concentrations of cholesterol precursor sterols and plant sterols vary over a 5- to 10-fold range among normolipidemic individuals, and provide indices of the relative rates of cholesterol synthesis and fractional absorption. In the present study, we examined the relative contributions of genetic and environmental factors to variation in the plasma concentrations and sterol-cholesterol ratios of five noncholesterol sterols, including the 5
Taken together, these findings indicate that variation in the plasma concentrations of noncholesterol sterols is highly heritable, and that polymorphism in ABCG8 contributes to genetic variation in the plasma concentrations of plant sterols. — Berge, K. E., K. von Bergmann, D. Lutjohann, R. Guerra, S. M. Grundy, H. H. Hobbs, and J. C. Cohen. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J. Lipid Res. 2002. 43: 486–494.
Supplementary key words:
sitosterol, cholesterol absorption, cholesterol synthesis
Copyright © 2002 by Lipid Research, Inc.
Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8
Knut E. Bergea,
Klaus von Bergmannd,
Dieter Lutjohannd,
Rudy Guerrae,
Scott M. Grundyc,
Helen H. Hobbsa,b, and
Jonathan C. Cohenb,c
a The Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390-9052
b The McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX 75390-9052
c The Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390-9052
d The Department of Clinical Pharmacology, University of Bonn, Bonn, Germany
e The Department of Statistics, Rice University, Houston, TX 77005
-saturated derivative of cholesterol (cholestanol), two precursors in the cholesterol biosynthesis pathway (desmosterol and lathosterol), and two phytosterols (campesterol and sitosterol). Plasma sterol concentrations were highly stable in 30 individuals measured over a 48 week period. Regression of offspring sterol levels on the parental values indicated that plasma levels of all five noncholesterol sterols were highly heritable. Analysis of monozygotic and dizygotic twin pairs also indicated strong heritability of all five sterols. Two common sequence variations (D19H and T400K) in ABCG8, an ABC half-transporter defective in sitosterolemia, were associated with lower concentrations of plant sterols in parents, and in their offspring. 
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