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

• Published in: International journal of clinical and experimental medicine Vol. 8; no. 4; pp. 5978 - 5988
• Main Authors: Zambrano, Tomás, Hirata, Mario Hiroyuki, Cerda, Álvaro, Dorea, Egidio L, Pinto, Gelba A, Gusukuma, Maria C, Bertolami, Marcelo C, Salazar, Luis A, Hirata, Rosario Dominguez Crespo
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 2015
• Subjects: Original; microRNAs; Atorvastatin; PCSK9; cholesterol; polymorphism; LDLR
• ISSN: 1940-5901; 1940-5901

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. 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. 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. 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.