title: HMGCR rs17671591 SNP Determines Lower Plasma LDL-C after Atorvastatin Therapy in Chilean Individuals.
abstract: Lipid-lowering response to statin therapy shows large interindividual variability. At a genome-wide significance level, single nucleotide polymorphisms (SNPs) in PCSK9 and HMGCR have been implicated in this differential response. However, the influence of these variants is uncertain in the Chilean population. Hence, we aimed to evaluate the contribution of PCSK9 rs7552841 and HMGCR rs17671591 SNPs as genetic determinants of atorvastatin response in Chilean hypercholesterolaemic individuals. One hundred and one hypercholesterolaemic patients received atorvastatin 10 mg/day for 4 weeks. Plasma lipid profile (TC, HDL-C, LDL-C and TG) was determined before and after statin treatment, and SNPs were identified by allelic discrimination using TaqMan(®) SNP Genotyping Assays. Adjusted univariate and multivariate analyses' models were used for statistical analyses, and a p-value <0.05 was considered significant. From baseline (week 0) to the study end-point (week 4), significant reductions were observed in plasma TC, LDL-C and TG (p < 0.001), while HDL-C levels were increased (p < 0.001). Multivariate analysis showed no association between lipid levels and atorvastatin therapy for the PCSK9 variant. However, the HMGCR rs17671591 T allele contributed to basal HDL-C concentration variability along with a higher increase in this lipid fraction after statin medication. In addition, this allele determined greater plasma LDL-C reductions after therapy with atorvastatin. Our data suggest that the HMGCR rs17671591 polymorphism can constitute a genetic marker of lower plasma LDL-C and enhanced HDL-C concentration after atorvastatin therapy in the Chilean population.
authors.affiliation: Center of Molecular Biology & Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresources Nucleus, University of La Frontera (BIOREN-UFRO), Temuco, Chile.|Preclinical Sciences Department, Faculty of Medicine, University of La Frontera, Temuco, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cuevas
authors.affiliation: Preclinical Sciences Department, Faculty of Medicine, University of La Frontera, Temuco, Chile.
authors.forename: César
authors.initials: C
authors.lastname: Fernández
authors.affiliation: Preclinical Sciences Department, Faculty of Medicine, University of La Frontera, Temuco, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Ferrada
authors.affiliation: Center of Molecular Biology & Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresources Nucleus, University of La Frontera (BIOREN-UFRO), Temuco, Chile.
authors.forename: Tomás
authors.initials: T
authors.lastname: Zambrano
authors.affiliation: Center of Molecular Biology & Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresources Nucleus, University of La Frontera (BIOREN-UFRO), Temuco, Chile.
authors.forename: Alexy
authors.initials: A
authors.lastname: Rosales
authors.affiliation: Center of Molecular Biology & Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresources Nucleus, University of La Frontera (BIOREN-UFRO), Temuco, Chile.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Saavedra
authors.affiliation: Center of Molecular Biology & Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresources Nucleus, University of La Frontera (BIOREN-UFRO), Temuco, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Salazar
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002677:Chile; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9 / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000069059:Atorvastatin; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9