Roelof Aj Smit1,2, Iris Postmus2, Stella Trompet1,2, Michael R Barnes3,4, Helen Warren3,4, Benoit J Arsenault5, Daniel I Chasman6,7, L Adrienne Cupples8,9, Graham A Hitman10, Ronald M Krauss11, Xiaohui Li12, Bruce M Psaty13,14, Charles M Stein15,16, Jerome I Rotter12, J Wouter Jukema1,17,18. 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.
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.
Authors: Jason S Simon; Maha C Karnoub; David J Devlin; Maria G Arreaza; Ping Qiu; Stephanie A Monks; Michael E Severino; Paul Deutsch; Joanne Palmisano; Alan B Sachs; Marvin L Bayne; Andrew S Plump; Eric E Schadt Journal: Genomics Date: 2005-11-16 Impact factor: 5.736
Authors: André J Tremblay; Benoît Lamarche; Valéry Lemelin; Lizbeth Hoos; Suzanne Benjannet; Nabil G Seidah; Harry R Davis; Patrick Couture Journal: J Lipid Res Date: 2010-12-01 Impact factor: 5.922
Authors: Margarita Garcia-Calvo; JeanMarie Lisnock; Herbert G Bull; Brian E Hawes; Duane A Burnett; Matthew P Braun; James H Crona; Harry R Davis; Dennis C Dean; Patricia A Detmers; Michael P Graziano; Meredith Hughes; D Euan Macintyre; Anthony Ogawa; Kim A O'neill; Sai Prasad N Iyer; Diane E Shevell; Marsha M Smith; Yui S Tang; Amanda M Makarewicz; Feroze Ujjainwalla; Scott W Altmann; Kevin T Chapman; Nancy A Thornberry Journal: Proc Natl Acad Sci U S A Date: 2005-05-31 Impact factor: 11.205
Authors: C Baigent; L Blackwell; J Emberson; L E Holland; C Reith; N Bhala; R Peto; E H Barnes; A Keech; J Simes; R Collins Journal: Lancet Date: 2010-11-08 Impact factor: 79.321
Authors: Iris Postmus; Stella Trompet; Harshal A Deshmukh; Michael R Barnes; Xiaohui Li; Helen R Warren; Daniel I Chasman; Kaixin Zhou; Benoit J Arsenault; Louise A Donnelly; Kerri L Wiggins; Christy L Avery; Paula Griffin; QiPing Feng; Kent D Taylor; Guo Li; Daniel S Evans; Albert V Smith; Catherine E de Keyser; Andrew D Johnson; Anton J M de Craen; David J Stott; Brendan M Buckley; Ian Ford; Rudi G J Westendorp; P Eline Slagboom; Naveed Sattar; Patricia B Munroe; Peter Sever; Neil Poulter; Alice Stanton; Denis C Shields; Eoin O'Brien; Sue Shaw-Hawkins; Y-D Ida Chen; Deborah A Nickerson; Joshua D Smith; Marie Pierre Dubé; S Matthijs Boekholdt; G Kees Hovingh; John J P Kastelein; Paul M McKeigue; John Betteridge; Andrew Neil; Paul N Durrington; Alex Doney; Fiona Carr; Andrew Morris; Mark I McCarthy; Leif Groop; Emma Ahlqvist; Joshua C Bis; Kenneth Rice; Nicholas L Smith; Thomas Lumley; Eric A Whitsel; Til Stürmer; Eric Boerwinkle; Julius S Ngwa; Christopher J O'Donnell; Ramachandran S Vasan; Wei-Qi Wei; Russell A Wilke; Ching-Ti Liu; Fangui Sun; Xiuqing Guo; Susan R Heckbert; Wendy Post; Nona Sotoodehnia; Alice M Arnold; Jeanette M Stafford; Jingzhong Ding; David M Herrington; Stephen B Kritchevsky; Gudny Eiriksdottir; Leonore J Launer; Tamara B Harris; Audrey Y Chu; Franco Giulianini; Jean G MacFadyen; Bryan J Barratt; Fredrik Nyberg; Bruno H Stricker; André G Uitterlinden; Albert Hofman; Fernando Rivadeneira; Valur Emilsson; Oscar H Franco; Paul M Ridker; Vilmundur Gudnason; Yongmei Liu; Joshua C Denny; Christie M Ballantyne; Jerome I Rotter; L Adrienne Cupples; Bruce M Psaty; Colin N A Palmer; Jean-Claude Tardif; Helen M Colhoun; Graham Hitman; Ronald M Krauss; J Wouter Jukema; Mark J Caulfield Journal: Nat Commun Date: 2014-10-28 Impact factor: 14.919