Next Article in Journal
Elevated Circulating TNF-α in Fat-Free Mass Non-Responders Compared to Responders Following Exercise Training in Older Women
Next Article in Special Issue
Cellular Localization and Trafficking of the Human ABCG1 Transporter
Previous Article in Journal
Vesicular Trafficking Defects, Developmental Abnormalities, and Alterations in the Cellular Death Process Occur in Cell Lines that Over-Express Dictyostelium GTPase, Rab2, and Rab2 Mutants
Article Menu

Export Article

Open AccessArticle
Biology 2014, 3(3), 536-550; doi:10.3390/biology3030536

Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate

1
USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
2
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA
3
Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA
4
Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
5
The Department of Epidemiology and Population Genetics. Centro Nacional Investigación Cardiovasculares (CNIC), Madrid 28029, Spain
6
IMDEA Food, Madrid 28049, Spain
7
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
8
Department of Laboratory Medicine and Pathology, University of Minnesota, MN55455, USA
9
Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, AL 35294, USA
10
Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, AL 35294, USA
*
Author to whom correspondence should be addressed.
Received: 23 June 2014 / Revised: 29 July 2014 / Accepted: 5 August 2014 / Published: 25 August 2014
(This article belongs to the Special Issue Lipid Metabolism)
View Full-Text   |   Download PDF [335 KB, uploaded 25 August 2014]   |  

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. View Full-Text
Keywords: pharmacogenetics; candidate gene study; lipoprotein; fenofibrate; NMR; GOLDN; genetic risk score; particle size; LDL size; HDL size pharmacogenetics; candidate gene study; lipoprotein; fenofibrate; NMR; GOLDN; genetic risk score; particle size; LDL size; HDL size
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Frazier-Wood, A.C.; Wojczynski, M.K.; Borecki, I.B.; Hopkins, P.N.; Lai, C.-Q.; Ordovas, J.M.; Straka, R.J.; Tsai, M.Y.; Tiwari, H.K.; Arnett, D.K. Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate. Biology 2014, 3, 536-550.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top