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.
*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.
Reprints: Ariel Brautbar, MD, Department of Medicine, Baylor College of Medicine, 6565 Fannin St, Houston, TX 77030 (e-mail: brautbar@bcm.edu).
Supported by Marshfield Clinic Research Foundation, generous donors to Marshfield Clinic, and the Clinical and Translational Science Award (CTSA) program, previously through the National Center for Research Resources (NCRR) grant 1UL1RR025011 and the National Center for Advancing Translational Sciences (NCATS) grant 9U54TR000021, and now by the NCATS grant UL1TR000427.
The authors report no conflicts of interest.
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Received July 29, 2014
Accepted March 23, 2015
