title: Differential Lipid Response to Statins Is Associated With Variants in the BUD13-APOA5 Gene Region.
abstract: Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for 3 SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P = 0.000159), whereas the minor allele at rs12806755 was associated with a similar response to lovastatin (P = 0.000192). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P = 0.000668) with some patients with the minor allele having LDL-C increase after therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population.
authors.affiliation: *Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI; †Health Services Research and Development, Michael E. DeBakey Veterans Affairs Medical Center and Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX; and ‡Division of Genetics and Endocrinology, Cook Children's Medical Center, Fort Worth, TX.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: OʼBrien
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schrodi
authors.forename: Zhan
authors.initials: Z
authors.lastname: Ye
authors.forename: Murray H
authors.initials: MH
authors.lastname: Brilliant
authors.forename: Salim S
authors.initials: SS
authors.lastname: Virani
authors.forename: Ariel
authors.initials: A
authors.lastname: Brautbar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; C000595434:BUD13 homolog protein, human; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016601:RNA-Binding Proteins; D014280:Triglycerides