Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

Alexis C. Frazier-Wood, Mary K. Wojczynski, Ingrid B. Borecki, Paul N. Hopkins, Chao Qiang Lai, Jose M. Ordovas, Robert J. Straka, Micheal Y. Tsai, Hemant K. Tiwari, Donna K. Arnett

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.

Original languageEnglish
Pages (from-to)536-550
Number of pages15
JournalBiology
Volume3
Issue number3
DOIs
StatePublished - Aug 25 2014

Keywords

  • Candidate gene study
  • Fenofibrate
  • GOLDN
  • Genetic risk score
  • HDL size
  • LDL size
  • Lipoprotein
  • NMR
  • Particle size
  • Pharmacogenetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Agricultural and Biological Sciences (all)

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