title: Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate.
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.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA. LekkiWood@Gmail.com.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. mwojczyn@dsgmail.wustl.edu.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. iborecki@wustl.edu.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA. paul.hopkins@utah.edu.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. chao.lai@tufts.edu.
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. jordov01@tufts.edu.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. strak001@umn.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Straka
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, MN55455, USA. tsaix001@umn.edu.
authors.forename: Micheal Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, AL 35294, USA. htiwari@uab.edu.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA. arnett@uab.edu.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett