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Papers In Press, published online ahead of print December 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600452-JLR200

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Journal of Lipid Research, Vol. 48, 2607-2613, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Single nucleotide polymorphisms in ABCG5 and ABCG8 are associated with changes in cholesterol metabolism during weight loss

Sylvia Santosa^*, Isabelle Demonty^*, Alice H. Lichtenstein, Jose M. Ordovas and Peter J. H. Jones^1,

^* School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada
Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of 2 tables.

Published, JLR Papers in Press, September 7, 2007.

¹ To whom correspondence should be addressed. e-mail: peter_jones{at}umanitoba.ca

The purpose of this study was to examine whether changes in cholesterol metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Thirty-five hypercholesterolemic women lost 11.7 ± 2.5 kg (P < 0.001). Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5/G8. Homozygous Q604E variants in ABCG5 had larger (P < 0.05) reductions in cholesterol absorption and greater increases (P < 0.05) in synthesis in contrast to heterozygous and homozygous wild-type carriers. Heterozygous C54Y carriers had smaller declines (P = 0.047) in synthesis compared with homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P = 0.042) post-weight-loss synthesis compared with carriers of the C54 genotype. The direction of the results is consistent with cross-sectional studies on the effects of Q604E and C54Y polymorphisms on plasma cholesterol. SNPs in ABCG5/G8 were found to be associated with the response of cholesterol metabolism to weight loss. The evidence for associations between SNPs in ABCG5/G8 and various parameters of cholesterol metabolism indicates the potential effectiveness of establishing genetic screening tools to determine optimal lipid-lowering treatment routes for individuals during weight reduction.

Supplementary key words lipids • metabolism • genetics • mutations • women • overweight • obesity • hypercholesterolemic • diet • physical activity

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