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Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men

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Lipids

Abstract

ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

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Acknowledgments

This project was supported by grants from Unilever R&D, Vlaardingen, the Netherlands, and by the Canadian Institutes of Health Research—Provincial Partnership Program. The authors thank Brian Sithoo for his technical support in SNP analysis and Iwona Rudkowska for her comments on discussion.

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Authors and Affiliations

  1. Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Drive, Winnipeg, MB, R3T 6C5, Canada

    Hai L. Zhao & Peter J. H. Jones

  2. School of Dietetics and Human Nutrition, McGill University, Sainte-Anne-de-Bellevue, QC, Canada

    Adrielle H. Houweling, Catherine A. Vanstone & Stephanie Jew

  3. Unilever Food and Health Research Institute, Unilever R&D, Vlaardingen, The Netherlands

    Elke A. Trautwein & Guus S. M. J. E. Duchateau

Authors
  1. Hai L. Zhao
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  2. Adrielle H. Houweling
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  3. Catherine A. Vanstone
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  4. Stephanie Jew
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  5. Elke A. Trautwein
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  6. Guus S. M. J. E. Duchateau
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  7. Peter J. H. Jones
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Correspondence to Peter J. H. Jones.

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Zhao, H.L., Houweling, A.H., Vanstone, C.A. et al. Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men. Lipids 43, 1155–1164 (2008). https://doi.org/10.1007/s11745-008-3241-y

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  • DOI: https://doi.org/10.1007/s11745-008-3241-y

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