title: Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study.
abstract: Plant sterol (PS) consumption decreases low-density lipoprotein cholesterol (LDL-C) levels; however, high variability of responsiveness of lipid levels to PS intervention has been observed. We hypothesized that common single-nucleotide polymorphisms (SNPs) in the genes for the ATP binding cassette proteins G5 (ABCG5) and G8 (ABCG8), Niemann-Pick C1-like 1 (NPC1L1), or other proteins of the cholesterol pathway, would underline inter-individual variations in response to PS. Twenty-six hyperlipidemic subjects completed a randomized trial of 3 PS phases and a control phase. Three non-responders were identified who failed on 3 consecutive occasions to decrease either total cholesterol or LDL-C level vs. control. It was observed that after 3 PS phases compared with a control phase, cholesterol absorption changed to a lesser degree (-7.7% +/- 10.8%) in the non-responders than in the top 3 responders (-22.1% +/- 8.8%); however, cholesterol synthesis rates did not differ between sub-groups. No common polymorphisms in ABCG8, ABCG5, or NPC1L1 were demonstrated between the 3 top responders and the non-responders. Yet, 1 non-responsive subject did demonstrate a rare SNP in NPC1L1. Results indicate PS intake did not decrease cholesterol absorption rates to the same degree in certain subjects, possibly clarifying the inter-individual variability in the cholesterol-lowering effect; hence, this work should be expanded.
authors.affiliation: School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, QC, Canada.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rudkowska
authors.forename: Suhad S
authors.initials: SS
authors.lastname: AbuMweis
authors.forename: Catherine
authors.initials: C
authors.lastname: Nicolle
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016037:Single-Blind Method
chemical_list: D008055:Lipids; D010840:Phytosterols; D002784:Cholesterol