J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600452-JLR200 on September 7, 2007

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 lossboxs

Sylvia Santosa*, Isabelle Demonty*, Alice H. Lichtenstein{dagger}, Jose M. Ordovas{dagger} and Peter J. H. Jones1,§

* School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada
{dagger} 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

boxs 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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