Submitted on October 11, 2006
Revised on September 6, 2007
Accepted on September 7, 2007
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
Mayo Clinic, Rochester, MN 55905
Corresponding Author: sylviasantosa{at}gmail.com
Objective: To examine whether changes in cholesterol 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. 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 to homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P=0.042) post-weight loss synthesis compared to 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. Conclusion: 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 in establishing genetic screening tools to determine optimal lipid lowering treatment routes for individuals during weight reduction.
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