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Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine.
De Castro-Orós, Isabel; Solà, Rosa; Valls, Rosa María; Brea, Angel; Mozas, Pilar; Puzo, Jose; Pocoví, Miguel.
Afiliação
  • De Castro-Orós I; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
  • Solà R; Unidad de Lípidos, Servicio de Medicina Interna, Hospital Universitario San Pedro, Logroño, Spain.
  • Valls RM; 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.
  • Brea A; Unidad de Lípidos, Servicio de Medicina Interna, Hospital Universitario San Pedro, Logroño, Spain.
  • Mozas P; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
  • Puzo J; Servicio de Bioquímica Clínica. Hospital Universitario Miguel Servet, Zaragoza, Spain.
  • Pocoví M; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
PLoS One ; 11(3): e0150785, 2016.
Article em En | MEDLINE | ID: mdl-27015087
ABSTRACT

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 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.

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 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).

CONCLUSIONS:

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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Berberina / Receptores de LDL / Serina Endopeptidases / Pró-Proteína Convertases / Hipercolesterolemia Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Berberina / Receptores de LDL / Serina Endopeptidases / Pró-Proteína Convertases / Hipercolesterolemia Idioma: En Ano de publicação: 2016 Tipo de documento: Article