Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study

Rudkowska, Iwona; AbuMweis, Suhad S.; Nicolle, Catherine; Jones, Peter J. H.
August 2008
Applied Physiology, Nutrition & Metabolism;Aug2008, Vol. 33 Issue 4, p728
Academic Journal
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. L’apport alimentaire de phytostérol (PS) diminue la concentration de cholestérol lié aux lipoprotéines de basse densité (LDL-C) ; néanmoins, des études signalent une grande variation des concentrations de lipides en réponse à un apport de PS. Nous avançons l’hypothèse selon laquelle des polymorphismes (SNP) mononucléotiques présents dans les transporteurs à cassettes se liant à l'ATP (ABCG5 et ABCG8), dans le Niemann-Pick C1 Like 1 (NPC1L1) ou dans d’autres gènes de la voie du cholestérol seraient à la base de cette variation des réponses à l’apport de PS. Vingt-six sujets hyperlipémiques participent à un essai randomisé comprenant trois périodes de PS et une période de contrôle. Nous identifions trois sujets qui, en trois occasions, ne présentent pas de diminution de cholestérol total ou de LDL-C, comparativement à la période de contrôle ; chez ces trois sujets, on remarque que l’absorption de cholestérol dans les périodes de PS varie moins (-7,7 % ± 10,8 %) que chez les trois sujets qui réagissent le plus (-22,1 % ± 8,8 %) au cours de ces périodes. Néanmoins, on n’observe pas de différences au plan de la synthèse de cholestérol chez ces deux sous-groupes. De plus, ces deux sous-groupes ne présentent pas de polymorphismes communs dans ABCG8, ABCG5 et NPC1L1. Pourtant, un sujet non réactif présente un SNP rare dans le gène NPC1L1. D’après nos observations, l’apport de PS ne diminue pas le taux d’absorption du cholestérol au même niveau chez certains sujets, ce qui expliquerait en partie la variation interindividuelle au plan de la diminution de la concentration de cholestérol. Dès lors, il faut faire d’autres études.


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