title: Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia.
abstract: 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.
  
  
  CONCLUSIONS
  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: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. brautbar@bcm.edu
authors: Ariel
authors: A
authors: Brautbar
authors: Daniel
authors: D
authors: Covarrubias
authors: John
authors: J
authors: Belmont
authors: Fremiet
authors: F
authors: Lara-Garduno
authors: Salim S
authors: SS
authors: Virani
authors: Peter H
authors: PH
authors: Jones
authors: Suzanne M
authors: SM
authors: Leal
authors: Christie M
authors: CM
authors: Ballantyne
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D015415:Biomarkers; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D011345:Fenofibrate