Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment

Author:

Smit Roelof AJ12,Postmus Iris2,Trompet Stella12,Barnes Michael R34,Warren Helen34,Arsenault Benoit J5,Chasman Daniel I67,Cupples L Adrienne89,Hitman Graham A10,Krauss Ronald M11,Li Xiaohui12,Psaty Bruce M1314,Stein Charles M1516,Rotter Jerome I12,Jukema J Wouter11718

Affiliation:

1. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

2. Section of Gerontology & Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

3. William Harvey Research Institute, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK

4. NIHR Barts Cardiovascular Biomedical Research Unit, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK

5. Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada

6. Division of Preventive Medicine, Brigham & Women's Hospital, Boston, MA 02215, USA

7. Harvard Medical School, Harvard University, Boston, MA 02115, USA

8. Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA

9. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702-5827, USA

10. Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London EC1M 6BQ, UK

11. Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA

12. Institute for Translational Genomics & Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA

13. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology & Health Services, University of Washington, Seattle, WA 98101, USA

14. Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA

15. Department of Medicine, Vanderbilt University, Nashville, TN 37232-6602, USA

16. Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA

17. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

18. Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands

Abstract

Aims: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response. Methods: We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia. Results: Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels. Conclusion: Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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