ArticlePharmacogenetics and genomics2012
Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate.
Article in Pharmacogenetics and genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity.Human genetics · 2013Trial
- Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance.Animals : an open access journal from MDPI · 2024Article
- Endothelial Cell Receptors in Tissue Lipid Uptake and Metabolism.Circulation research · 2021Review
- Fibrate pharmacogenomics: expanding past the genome.Pharmacogenomics · 2020Article
- Genome-wide association study identifies QTLs for displacement of abomasum in Chinese Holstein cattle1.Journal of animal science · 2019Article
- Efficient Software for Multi-marker, Region-Based Analysis of GWAS Data.G3 (Bethesda, Md.) · 2016Article
- A family-specific linkage analysis of blood lipid response to fenofibrate in the Genetics of Lipid Lowering Drug and Diet Network.Pharmacogenetics and genomics · 2015Article
- Article
- Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression.The Journal of biological chemistry · 2014Article
- Pharmacogenomics of high-density lipoprotein-cholesterol-raising therapies.Expert review of cardiovascular therapy · 2013Review
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveA shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyceridemia, simultaneously reduces IR and shifts in lipoprotein diameter. Individual responses to fenofibrate vary, and we conducted a genome-wide association study to identify genetic differences that could contribute to such differences.
methodsAssociation analysis was conducted between single nucleotide polymorphisms (SNPs) on the Affymetrix 6.0 array and fasting particle diameter responses to a 12-week fenofibrate trial, in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network. Linear models were conducted, which adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. The top three SNPs associated with each fraction were examined subsequently for associations with changes in subfraction concentrations.
resultsSNPs in AHCYL2 and CD36 genes reached, or closely approached, genome-wide levels of significance with VLDL and HDL diameter responses to fenofibrate, respectively (P=4×10(-9) and 8×10(-8)). SNPs in AHCYL2 were associated with a decrease in the concentration of the large VLDL subfraction only (P=0.002). SNPs associated with HDL diameter change were not associated with a single subfraction concentration change (P>0.05) indicating small shifts across all subfractions.
conclusionWe report novel associations between lipoprotein diameter responses to fenofibrate and the AHCYL2 and CD36 genes. Previous associations of these genes with IR emphasize the role of IR in mediating lipoprotein response to fenofibrate.
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