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

The Pharmacogenomics Journal volume 13, pages 430–436 (2013)Cite this article

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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, PFDR=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), PFDR=0.03). Our findings support that KCNJ1 variation is associated with HCTZ-induced dysglycemia and NOD.

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Acknowledgements

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. 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. The project described was supported by Award Number TL1RR029888 from the National Center for Research Resources (JH Karnes). We thank Brian Gawronski, Ben Burkley, Lynda Stauffer and Cheryl Galloway for processing and genotyping samples, the PEAR study physicians Drs George Baramidze, Carmen Bray, Kendall Campbell, R Whit Curry, Frederic Rabari-Oskoui, Dan Rubin and Seigfried Schmidt, and the patients who participated in PEAR and INVEST-GENES.

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Authors and Affiliations

  1. Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, FL, USA

    J H Karnes, C W McDonough, Y Gong, T T Vo, T Y Langaee, J G Gums, J A Johnson & R M Cooper-DeHoff

  2. Renal Division, Emory University School of Medicine, Atlanta, GA, USA

    A B Chapman & S T Turner

  3. Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL, USA

    J G Gums, C J Pepine, J A Johnson & R M Cooper-DeHoff

  4. Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA

    A L Beitelshees

  5. Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, MN, USA

    K R Bailey

  6. Division of Epidemiology, Center for Human Genetics, University of Texas at Houston School of Public Health, Houston, TX, USA

    J L Del-Aguila & E A Boerwinkle

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  1. J H Karnes
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Correspondence to R M Cooper-DeHoff.

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Competing interests

Drs Johnson, Pepine, Cooper-DeHoff and Langaee have received funding from Abbott Laboratories. The other authors declare no conflict of interest.

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Karnes, J., McDonough, C., Gong, Y. et al. Association of KCNJ1 variation with change in fasting glucose and new onset diabetes during HCTZ treatment. Pharmacogenomics J 13, 430–436 (2013). https://doi.org/10.1038/tpj.2012.34

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