title: Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes.
abstract: Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.
authors.affiliation: Department of Epidemiology, University of Washington Seattle, WA, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Suchy-Dicey
authors.affiliation: Department of Epidemiology, University of Washington Seattle, WA, USA ; Department of Pharmacy, University of Washington Seattle, WA, USA ; Group Health Research Institute, Group Health Cooperative Seattle, WA, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Department of Epidemiology, University of Washington Seattle, WA, USA ; Group Health Research Institute, Group Health Cooperative Seattle, WA, USA ; Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development Seattle, WA, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Department of Biostatistics, University of Washington Seattle, WA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center Torrance, CA, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center Torrance, CA, USA.
authors.forename: Yd Ida
authors.initials: YI
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, University of Washington Seattle, WA, USA ; Department of Health Services, University of Washington Seattle, WA, USA ; Department of Medicine, University of Washington Seattle, WA, USA ; Group Health Research Institute, Group Health Cooperative Seattle, WA, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Epidemiology, University of Washington Seattle, WA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Enquobahrie
keywords: Type 2 diabetes; chemokine ligand 14; gene expression; microarray; statins; supervised normalization; surrogate variable analysis; thiazide diuretics; whole blood; zinc finger proteins