Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

J Med Genet. 2016 Dec;53(12):835-845. doi: 10.1136/jmedgenet-2016-103966. Epub 2016 Sep 1.

Abstract

Background: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.

Methods and results: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10-4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10-8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.

Conclusions: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.

Keywords: Genome-wide association study; HDL-cholesterol; Statins; pharmacogenetics.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol Ester Transfer Proteins / genetics*
  • Cholesterol, HDL / drug effects
  • Cholesterol, HDL / genetics*
  • Cholesterol, HDL / metabolism
  • European Continental Ancestry Group / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome

Substances

  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Grant support