title: Single nucleotide polymorphisms in ABCG5 and ABCG8 are associated with changes in cholesterol metabolism during weight loss.
abstract: 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.
authors.affiliation: School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Santosa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Demonty
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Jones
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015431:Weight Loss / Q000235:genetics*