ARS | Publication request: Single Nucleotide Polymorphisms in ABCG5 and ABCG8 are associated with changes in cholestrol metabolism during weight loss

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 7, 2007
Publication Date: December 1, 2007
Citation: Santosa, S., Demonty, I., Lichtenstein, A.H., Ordovas, J.M., Jones, P.J. 2007. Single Nucleotide Polymorphisms in ABCG5 and ABCG8 are associated with changes in cholestrol metabolism during weight loss. Journal of Lipid Research. 48(12):2607-2613.

Interpretive Summary: Objective: To examine whether changes in cholesterol lowering and metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Methods and Results: Thirty-five hypercholesterolemic women lost 11.7 kg. Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5 and ABCG8. Individuals heterozygous for D19H in ABCG8 had lower initial TC and LDL-C levels, and post- weight loss LDL-C values than homozygous D19 individuals. Carriers of at least one C54Y variant in ABCG8 had higher post-weight loss LDL-C values compared with homozygous wild types. Homozygous Q604E variants in ABCG5 had larger reductions in cholesterol absorption and greater increases in synthesis in contrast to heterozygous and homozygous wild type carriers. Heterozygous C54Y carriers had attenuated declines in synthesis compared to homozygous mutant individuals. Subjects with at least one Y54 variant had higher post-weight loss synthesis in relation to C54 carriers.

Technical Abstract: Objective: To examine whether changes in cholesterol lowering and metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Methods and Results: 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. Individuals heterozygous for D19H in ABCG8 had lower (P<0.05) initial TC and LDL-C levels, and post- weight loss LDL-C values than homozygous D19 individuals. Carriers of at least one C54Y variant in ABCG8 had higher (P=0.047) post-weight loss LDL-C values compared with homozygous wild types. Homozygous Q604E variants in ABCG5 had larger (P<0.05) reductions in cholesterol absorption and greater increases in synthesis in contrast to heterozygous and homozygous wild type carriers. Heterozygous C54Y carriers had attenuated declines (P=0.047) in synthesis compared to homozygous mutant individuals. Subjects with at least one Y54 variant had higher (P=0.042) post-weight loss synthesis in relation to C54 carriers.