Listed in Issue 275


DE CASTRO-ORÓS and COLLEAGUES, 1. Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; 2. Unidad de Lípidos, Servicio de Medicina Interna, Hospital Universitario San Pedro, Logroño, Spain; 3. Unitat de Recerca de Lipids i Arteriosclerosi, CIBERDEM, Servei de Medicina Interna, Hospital Universitari San Joan, IISPV Facultat de Medicina, Universitat Rovira i Virgili, Reus, Spain; 4. Servicio de Bioquímica Clínica. Hospital Universitario Miguel Servet, Zaragoza, Spain studied using sequencing variations in response to antihypercholesterolemic effects of Armolipid Plus with Berberine.


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 inter-individual 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.


The authors sequenced the LDLR 3' and 5' untranslated regions (UTR) and the PCSK9 5' 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.


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 5' UTR and rs14158 (c.*52G>A) in the LDLR 3' 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).


Three polymorphisms in the 3' UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5' 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.


De Castro-Orós I1, Solà R2, Valls RM3, Brea A2, Mozas P1, Puzo J4, Pocoví M1. Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine. PLoS One. 11(3):e0150785. Mar 25 2016. doi: 10.1371/journal.pone.0150785. eCollection 2016.

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