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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #319171
Title: Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

Author
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item WOJCZYNSKI, MARY - Washington University School Of Medicine
item BORECKI, INGRID - Washington University School Of Medicine
item HOPKINS, PAUL - University Of Utah
item LAI, CHAO-QIANG - Tufts University
item ORDOVAS, JOSE - Tufts University
item STRAKA, ROBERT - University Of Minnesota
item TSAI, MICHEAL - University Of Minnesota
item TIWARI, HEMANT - University Of Alabama
item ARNETT, DONNA - University Of Alabama

Submitted to: Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2014
Publication Date: 8/25/2014
Citation: Frazier-Wood, A.C., Wojczynski, M.K., Borecki, I.B., Hopkins, P.N., Lai, C., Ordovas, J.M., Straka, R.J., Tsai, M.Y., Tiwari, H.K., Arnett, D.K. 2014. Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate. Biology. 3(3):536-550.

Interpretive Summary: Lipoproteins are particles that carry cholesterol in the blood to either be destroyed by the body or deposited as a fatty plaque in the arteries. Differences in sizes of the lipoproteins indicate differential risk for depositing cholesterol and plaques and as the plaques are associated with cardiovascular disease, different sizes of lipoproteins indicate different levels of cardiovascular disease risk. We constructed genetic risk scores that represented the total known genetic variation contributing to lipoprotein size, and examined whether these scores also associated with thow lipoprotein sizes change in response to fenofibrate (a drug similar to a statin). We found that the scores were not associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoproteins with fenofibrate treatment are not mediated by the genetic risk for lipoprotein levels and to understand different responses to fenofibrate treatment we need to look at other variants.

Technical 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.