title: LPL gene variants affect apoC-III response to combination therapy of statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia.
abstract: ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants (n = 1,250) in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Multivariate linear regression and two-way ANOVA for percent change in apoC-III level were performed. SNPs in the lipoprotein lipase (LPL) gene region, rs1801177 (P = 4.7 × 10(-8)), rs7016529 (P = 1.2 × 10(-6)), and rs249 (P = 4.1 × 10(-5)), were associated with apoC-III response to combination therapy. A haplotype composed of the minor alleles of these SNPs, with 2% population frequency, was associated with an unexpected apoC-III increase in response to statins and FA. This is the first report to show that genetic variation within the LPL gene region can affect the response of apoC-III levels to combined statin and FA therapy.
authors.affiliation: Department of Medical Genetics, Marshfield Clinic, Marshfield, WI; Sections of Cardiovascular Research and Cardiology, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. Electronic address: brautbar@bcm.edu.
authors.forename: Ariel
authors.initials: A
authors.lastname: Brautbar
authors.affiliation: Sections of Cardiovascular Research and Cardiology, Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX; and; Health Policy and Quality Program, Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, Houston, TX.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Virani
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
authors.forename: John
authors.initials: J
authors.lastname: Belmont
authors.affiliation: Sections of Cardiovascular Research and Cardiology, Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX; and.
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.affiliation: Sections of Cardiovascular Research and Cardiology, Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX; and.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Jones
authors.affiliation: Sections of Cardiovascular Research and Cardiology, Baylor College of Medicine, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX; and; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX; and.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: D053305:Apolipoprotein C-III / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D053305:Apolipoprotein C-III; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; C006012:fenofibric acid; D008071:Lipoprotein Lipase; D011345:Fenofibrate