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

International Journal of Clinical and Experimental Medicine

Mario Hiroyuki Hirata¹  Marcelo C Bertolami¹  Álvaro Cerda¹  Maria C Gusukuma¹  Egidio L Dorea¹  Rosario Dominguez Crespo Hirata¹  Gelba A Pinto¹  Tomás Zambrano¹  Luis A Salazar¹ 

关键词: Atorvastatin;    cholesterol;    LDLR;    PCSK9;    polymorphism;    microRNAs;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown