1. Genetic Variants in <italic>HSD17B3</italic>, <italic>SMAD3</italic>, and <italic>IPO11</italic> Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.
- Author
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Rotroff, Daniel M., Pijut, Sonja S., Marvel, Skylar W., Jack, John R., Havener, Tammy M., Pujol, Aurora, Schluter, Agatha, Graf, Gregory A., Ginsberg, Henry N., Shah, Hetal S., Gao, He, Morieri, Mario‐Luca, Doria, Alessandro, Mychaleckyi, Josyf C., McLeod, Howard L., Buse, John B., Wagner, Michael J., Motsinger‐Reif, Alison A., and the ACCORD/ACCORDion Investigators
- Subjects
HUMAN genetic variation ,LIPIDS ,TYPE 2 diabetes ,FENOFIBRATE ,CARDIOVASCULAR diseases risk factors ,GENOMICS ,GENE expression ,LABORATORY mice - Abstract
Individuals 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 andIPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10‐6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach.AKR7A3 andHSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions inHsd17b13 gene expression (q < 0.1). Associations of variants inSMAD3 ,IPO11 , andHSD17B13 , with gene expression changes in mice indicate that transforming growth factor‐beta (TGF‐β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D. [ABSTRACT FROM AUTHOR]- Published
- 2018
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