Impact of 3'UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: a pilot study
Int J Clin Exp Med
; 8(4): 5978-5988, 2015. tab
Artigo
em Inglês
| Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1063489
Biblioteca responsável:
BR79.1
Localização: BR79.1
ABSTRACT
BACKGROUND:
Hypercholesterolemia is a complex trait, resulting from a genetic interaction with lifestyle habits. Polymorphisms are a major source of genetic heterogeneity, and variations in 2 key cholesterol homeostasis genes; low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type-9 (PCSK9), lead to dyslipidemia. So, we investigated the relation of 2 variants located in the 3'-UTR (3'-untranslated region) of LDLR (rs14158, G>A) and PCSK9 (rs17111557, C>T) with lipid profile and atorvastatin response.METHODS:
SNP influence on lipid profile was assessed in hypercholesterolemic patients (HC; n = 89) using atorvastatin (10 mg/day/4 weeks) and in normolipidemic subjects (NL; n = 171). Genotyping was completed through real-time PCR using TaqMan assays.RESULTS:
rs14158 G allele was higher in HC than in NL group (P = 0.043). NL subjects carrying the T allele of the PCSK9 variant had lower high-density lipoprotein cholesterol (HDL-c) than C allele carriers (P = 0.009). There was no association between LDLR and PCSK9 SNPs and atorvastatin response. Additionally, the PCSK9 variant creates a microRNA interaction site, which could implicate an epigenetic mechanism in PCSK9-dependent HDL-C regulation.CONCLUSIONS:
The rs14158 SNP contributes to hypercholesterolemia. Also, a putative microRNA regulation may influence HDL-C variability observed in rs17111557 carriers. Cholesterol-lowering response to atorvastatin is not influenced by LDLR and PCSK9 variants.
Texto completo:
Disponível
Coleções:
Bases de dados nacionais
/
Brasil
Base de dados:
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Assunto principal:
Colesterol
/
MicroRNAs
/
Atorvastatina
País/Região como assunto:
América do Sul
/
Brasil
Idioma:
Inglês
Revista:
Int J Clin Exp Med
Ano de publicação:
2015
Tipo de documento:
Artigo
Instituição/País de afiliação:
Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera/CL
/
Institute Dante Pazzanese of Cardiology/BR
/
School of Pharmaceutical Sciences, University of São Paulo/BR
/
University Hospital, University of São Paulo/BR