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ESR1 polymorphisms and statin therapy: a sex-specific approach

The Pharmacogenomics Journal volume 16, pages 507–513 (2016)Cite this article

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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.

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Acknowledgements

We thank the Centro de Diagnóstico Cardiológico staff for their assistance in sample collection. We also thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brazil), REUNI/UFCSPA scholarship program, PROAP-CAPES, PRONEX-FAPERGS/CNPq, DECIT/SCTIE-MS/CNPq and FAPERGS for their financial support.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA, Porto Alegre, Brazil

    L Smiderle, M Fiegenbaum & S Almeida

  2. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA, Porto Alegre, Brazil

    M Fiegenbaum & S Almeida

  3. Departamento de Genética, Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, Brazil

    M H Hutz

  4. Centro de Diagnóstico Cardiológico, Porto Alegre, Brazil

    C R Van Der Sand, L C Van Der Sand, M E W Ferreira & R C Pires

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  1. L Smiderle
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Smiderle, L., Fiegenbaum, M., Hutz, M. et al. ESR1 polymorphisms and statin therapy: a sex-specific approach. Pharmacogenomics J 16, 507–513 (2016). https://doi.org/10.1038/tpj.2015.60

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