Genetic variants of LDLR and PCSK9 associated with variations in response to antihypercholesterolemic effects of Armolipid Plus with berberine

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Abstract

© 2016 De Castro-Orós et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms. Material and Methods: We sequenced the LDLR 30 and 50 untranslated regions (UTR) and the PCSK9 50 UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo. Results: Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C > G) in the PCSK9 50 UTR and rs14158 (c. ∗ 52G > A) in the LDLR 30 UTR explained 14.1%and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5%of this variability (p < 0.004). Conclusions: Three polymorphisms in the 30 UTR region of LDLR, c. ∗ 52G > A, c. ∗ 504G > A, and c. ∗ 773A > G, and two at the 50 UTR region of PCSK9, c.-3383C > G and c.-2063A > G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP.

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De Castro-Orós, I., Solà, R., Valls, R. M., Brea, A., Mozas, P., Puzo, J., & Pocoví, M. (2016). Genetic variants of LDLR and PCSK9 associated with variations in response to antihypercholesterolemic effects of Armolipid Plus with berberine. PLoS ONE, 11(3). https://doi.org/10.1371/journal.pone.0150785

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