1. ESR1 polymorphisms and statin therapy: a sex-specific approach.
- Author
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Smiderle L, Fiegenbaum M, Hutz MH, Van Der Sand CR, Van Der Sand LC, Ferreira ME, Pires RC, and Almeida S
- Subjects
- Aged, Biomarkers blood, Brazil, Female, Gene Frequency, Haplotypes, Humans, Hypercholesterolemia blood, Hypercholesterolemia genetics, Linkage Disequilibrium, Male, Middle Aged, Pharmacogenetics, Phenotype, Prospective Studies, Sex Factors, Treatment Outcome, Atorvastatin therapeutic use, Estrogen Receptor alpha genetics, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia drug therapy, Lipids blood, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Simvastatin therapeutic use
- Abstract
Lipid-lowering therapy has shown a high degree of variability in clinical response and there is evidence that the variability in drug response between individuals is due to genetic factors. Thirteen single nucleotide polymorphisms (SNPs) within the ESR1 gene were evaluated with basal lipid and lipoprotein levels, as well as response to lipid-lowering therapy, in 495 hypercholesterolemic individuals of European descent receiving simvastatin or atorvastatin. Significant associations were detected between rs4870061 (P=0.040, corrected P-value (PC)=0.440), rs1801132 (P=0.002, PC=0.022) and the SNP rs3020314 (P=0.013, PC=0.143) with triglyceride (TG) baseline levels. The rs4870061 was also associated with high-density lipoprotein cholesterol (HDL-C) baseline levels (P=0.045, PC=0.495). Regarding statin efficacy, rs2234693 C/C was associated with greater HDL-C increase (P=0.037; PC=0.407) and rs3798577 T allele was associated with greater total cholesterol (TC) reduction (P=0.019; PC=0.209) and greater TG reduction (P=0.026; PC=0.286). These associations suggest that ESR1 polymorphisms are in part responsible for the TC, HDL-C and TG variation levels and this effect may be sex-specific.
- Published
- 2016
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