OBJECTIVE:Atherogenic dyslipidemia is highly associated with coronary heart disease and is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol (LDL-C). The combination of statins and fibrates is a common modality to treat individuals with atherogenic dyslipidemia. We sought to identify single nucleotide polymorphisms (SNPs) associated with HDL-C, TG, and apolipoprotein A1 (ApoA-I) response to combination therapy with statins and fenofibric acid (FA) in individuals with atherogenic dyslipidemia. METHODS:2228 individuals with mixed dyslipidemia who were participating in a multicenter, randomized, double-blind, active-controlled study comparing FA alone, in combination with a statin, or statin alone for a 12-week period, were genotyped for 304 candidate SNPs. A multivariate linear regression analysis for percent change in HDL-C, ApoA-I and TG levels was performed. RESULTS: SNPs in the apolipoprotein (APO) A5-ZNF259 region rs3741298 (P = 1.8 × 10(-7)), rs964184 (P = 3.6 × 10(-6)), rs651821 (P = 4.5 × 10(-5)), and rs10750097 (P = 1 × 10(-4)), were significantly associated with HDL-C response to combination therapy with statins and FA, with a similar association identified for ApoA-I. A haplotype composed of the minor alleles of SNPs rs3741298, rs964184, and rs10750097, was associated with a positive response to statins and FA (P = 8.7 × 10(-7)) and had a frequency of 18% in the study population. CONCLUSION: In a population with atherogenic dyslipidemia, common SNPs and haplotypes within the APOA5-ZNF259 region are highly associated with HDL-C and ApoA-I response to combination therapy with statins and FA.
RCT Entities:
OBJECTIVE:Atherogenic dyslipidemia is highly associated with coronary heart disease and is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol (LDL-C). The combination of statins and fibrates is a common modality to treat individuals with atherogenic dyslipidemia. We sought to identify single nucleotide polymorphisms (SNPs) associated with HDL-C, TG, and apolipoprotein A1 (ApoA-I) response to combination therapy with statins and fenofibric acid (FA) in individuals with atherogenic dyslipidemia. METHODS: 2228 individuals with mixed dyslipidemia who were participating in a multicenter, randomized, double-blind, active-controlled study comparing FA alone, in combination with a statin, or statin alone for a 12-week period, were genotyped for 304 candidate SNPs. A multivariate linear regression analysis for percent change in HDL-C, ApoA-I and TG levels was performed. RESULTS: SNPs in the apolipoprotein (APO) A5-ZNF259 region rs3741298 (P = 1.8 × 10(-7)), rs964184 (P = 3.6 × 10(-6)), rs651821 (P = 4.5 × 10(-5)), and rs10750097 (P = 1 × 10(-4)), were significantly associated with HDL-C response to combination therapy with statins and FA, with a similar association identified for ApoA-I. A haplotype composed of the minor alleles of SNPs rs3741298, rs964184, and rs10750097, was associated with a positive response to statins and FA (P = 8.7 × 10(-7)) and had a frequency of 18% in the study population. CONCLUSION: In a population with atherogenic dyslipidemia, common SNPs and haplotypes within the APOA5-ZNF259 region are highly associated with HDL-C and ApoA-I response to combination therapy with statins and FA.
Authors: Christopher T Johansen; Jian Wang; Matthew B Lanktree; Henian Cao; Adam D McIntyre; Matthew R Ban; Rebecca A Martins; Brooke A Kennedy; Reina G Hassell; Maartje E Visser; Stephen M Schwartz; Benjamin F Voight; Roberto Elosua; Veikko Salomaa; Christopher J O'Donnell; Geesje M Dallinga-Thie; Sonia S Anand; Salim Yusuf; Murray W Huff; Sekar Kathiresan; Robert A Hegele Journal: Nat Genet Date: 2010-07-25 Impact factor: 38.330
Authors: Peter H Jones; Michael H Davidson; Moti L Kashyap; Maureen T Kelly; Susan M Buttler; Carolyn M Setze; Darryl J Sleep; James C Stolzenbach Journal: Atherosclerosis Date: 2008-10-05 Impact factor: 5.162
Authors: Alexander Thompson; Emanuele Di Angelantonio; Nadeem Sarwar; Sebhat Erqou; Danish Saleheen; Robin P F Dullaart; Bernard Keavney; Zheng Ye; John Danesh Journal: JAMA Date: 2008-06-18 Impact factor: 56.272
Authors: Peter H Jones; Harold E Bays; Michael H Davidson; Maureen T Kelly; Susan M Buttler; Carolyn M Setze; Darryl J Sleep; James C Stolzenbach Journal: Clin Drug Investig Date: 2008 Impact factor: 2.859
Authors: Jian Wang; Matthew R Ban; Brooke A Kennedy; Sonia Anand; Salim Yusuf; Murray W Huff; Rebecca L Pollex; Robert A Hegele Journal: Nat Clin Pract Cardiovasc Med Date: 2008-09-09
Authors: Pirkka-Pekka Laurila; Jussi Naukkarinen; Kati Kristiansson; Samuli Ripatti; Tuuli Kauttu; Kaisa Silander; Veikko Salomaa; Markus Perola; Pekka J Karhunen; Philip J Barter; Christian Ehnholm; Leena Peltonen Journal: Arterioscler Thromb Vasc Biol Date: 2009-11-12 Impact factor: 8.311
Authors: Russell Scott; Richard O'Brien; Greg Fulcher; Chris Pardy; Michael D'Emden; Dana Tse; Marja-Riitta Taskinen; Christian Ehnholm; Anthony Keech Journal: Diabetes Care Date: 2008-11-04 Impact factor: 19.112
Authors: Cristen J Willer; Serena Sanna; Anne U Jackson; Angelo Scuteri; Lori L Bonnycastle; Robert Clarke; Simon C Heath; Nicholas J Timpson; Samer S Najjar; Heather M Stringham; James Strait; William L Duren; Andrea Maschio; Fabio Busonero; Antonella Mulas; Giuseppe Albai; Amy J Swift; Mario A Morken; Narisu Narisu; Derrick Bennett; Sarah Parish; Haiqing Shen; Pilar Galan; Pierre Meneton; Serge Hercberg; Diana Zelenika; Wei-Min Chen; Yun Li; Laura J Scott; Paul A Scheet; Jouko Sundvall; Richard M Watanabe; Ramaiah Nagaraja; Shah Ebrahim; Debbie A Lawlor; Yoav Ben-Shlomo; George Davey-Smith; Alan R Shuldiner; Rory Collins; Richard N Bergman; Manuela Uda; Jaakko Tuomilehto; Antonio Cao; Francis S Collins; Edward Lakatta; G Mark Lathrop; Michael Boehnke; David Schlessinger; Karen L Mohlke; Gonçalo R Abecasis Journal: Nat Genet Date: 2008-01-13 Impact factor: 38.330
Authors: Ariel Brautbar; Salim S Virani; John Belmont; Vijay Nambi; Peter H Jones; Christie M Ballantyne Journal: J Lipid Res Date: 2012-01-11 Impact factor: 5.922