Rotroff, Daniel M.Pijut, Sonja S.Skylar W.Jack, John R.Havener, Tammy M.Pujol Onofre, AuroraSchlüter, AgathaGraf, Gregory A.Ginsberg, Henry N.Shah, Hetal S.Gao, HeMorieri, Mario-LucaDoria, AlessandroMychaleckyi, Josyf C.Mcleod, Howard L.Buse, John B.Wagner, Michael J.Motsinger-Reif, Alison A.ACCORD/ACCORDion Investigators2020-12-162020-12-162018-04-01https://hdl.handle.net/2445/172753Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 x 10(-6)). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D.10 p.application/pdfeng(c) American Society for Clinical Pharmacology and Therapeutics, 2018DiabetisDiabetesinfo:eu-repo/semantics/article2020-12-02info:eu-repo/semantics/openAccess28736931