Association of KCNJ1 variation with change in fasting glucose and new onset diabetes during HCTZ treatment

• Type of Material: Article
• Authors: J.H. Karnes, University of Florida; C.W. McDonough, University of Florida; Y. Gong, University of Florida; T.T. Vo, University of Florida; T.Y. Langaee, University of Florida; Arlene B Chapman, Emory University; J.G. Gums, University of Florida; A.L. Beitelshees, University of Maryland; K.R. Bailey, Mayo Clinic College of Medicine; J.L. Del-Aguila, University of Texas; E.A. Boerwinkle, University of Texas; C.J. Pepine, University of Florida; S.T. Turner, Emory University; J.A. Johnson, University of Florida; R.M. Cooper-DeHoff, University of Florida
• Language: English
• Date: 2013-10-01
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Macmillan Publishers Limited All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/tpj.2012.34
• Title of Journal or Parent Work: Pharmacogenomics Journal
• ISSN: 1470-269X
• Volume: 13
• Issue: 5
• Start Page: 430
• End Page: 436
• Grant/Funding Information: This work is supported by a grant from the National Institutes of Health (Bethesda, MD, USA), grant U01 GM074492, funded as part of the Pharmacogenetics Research Network.; The project described was supported by Award Number TL1RR029888 from the National Center for Research Resources (JH Karnes).; Additional support for this work includes: National Institutes of Health grants R01 HL74730, K23 grants HL091120 (AL Beitelshees) and HL086558 (RM Cooper-DeHoff); NIH CTSA grants UL1-RR092890 (University of Florida), UL1-RR025008 (Emory University) and UL1-RR024150 (Mayo Clinic); and grants from Abbott Laboratories, the University of Florida Opportunity Fund. and the Mayo Foundation.
• Keywords: diabetes mellitus; HYPERTENSIVE SUBJECTS; MELLITUS; Pharmacology & Pharmacy; TRIAL; THIAZIDE DIURETICS; BLOOD-PRESSURE; INVEST; hypertension; Genetics & Heredity; Science & Technology; pharmacogenetics; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR EVENTS; POTASSIUM; VERAPAMIL SR-TRANDOLAPRIL; ROMK1; hydrochlorothiazide; Life Sciences & Biomedicine; KCNJ1
• Research Categories: Health Sciences, Pharmacology; Biology, Genetics; Health Sciences, Nutrition

Abstract

Thiazide-induced potassium loss may contribute to new onset diabetes (NOD). KCNJ1 encodes a potassium channel and one study observed that a KCNJ1 single-nucleotide polymorphism (SNP) was associated with changes in fasting glucose (FG) during hydrochlorothiazide (HCTZ) treatment. We used linear regression to test association of KCNJ1 SNPs and haplotypes with FG changes during HCTZ treatment in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. We used logistic regression to test association of KCNJ1 variation with NOD in HCTZ-treated patients from the International Verapamil SR Trandolapril Study (INVEST). Multivariate regression analyses were performed by race/ethnicity with false discovery rate (FDR) correction. In PEAR blacks, a KCNJ1 SNP was associated with increased FG during HCTZ treatment (beta=8.47, P FDR =0.009). KCNJ1 SNPs and haplotypes were associated with NOD risk in all INVEST race/ethnic groups (strongest association: odds ratio 2.14 (1.31-3.53), P FDR =0.03). Our findings support that KCNJ1 variation is associated with HCTZ-induced dysglycemia and NOD.