Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Floyd, J.S. et al. (2018) Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics Journal, 18(1), pp. 127-135. (doi:10.1038/tpj.2016.90) (PMID:27958378) (PMCID:PMC5468495)

[img]
Preview
Text
135918.pdf - Accepted Version

910kB
[img]
Preview
Text
135918Suppl.pdf - Supplemental Material

358kB

Abstract

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Sattar, Professor Naveed
Authors: Floyd, J.S., Sitlani, C.M., Avery, C.L., Noordam, R., Li, X., Smith, A.V., Gogarten, S.M., Li, J., Broer, L., Evans, D.S., Trompet, S., Brody, J.A., Stewart, J.D., Eicher, J.D., Seyerle, A.A., Roach, J., Lange, L.A., Lin, H.J., Kors, J.A., Harris, T.B., Li-Gao, R., Sattar, N., Cummings, S.R., Wiggins, K.L., Napier, M.D., Stürmer, T., Bis, J.C., Kerr, K.F., Uitterlinden, A.G., Taylor, K.D., Stott, D.J., de Mutsert, R., Launer, L.J., Busch, E.L., Méndez-Giráldez, R., Sotoodehnia, N., Soliman, E.Z., Li, Y., Duan, Q., Rosendaal, F.R., Slagboom, P.E., Wilhelmsen, K.C., Reiner, A.P., Chen, Y.-D., Heckbert, S.R., Kaplan, R.C., Rice, K.M., Jukema, J.W., Johnson, A.D., Liu, Y., Mook-Kanamori, D.O., Gudnason, V., Wilson, J.G., Rotter, J.I., Laurie, C.C., Psaty, B.M., Whitsel, E.A., Cupples, L.A., and Stricker, B.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pharmacogenomics Journal
Publisher:Nature Publishing Group
ISSN:1470-269X
ISSN (Online):1473-1150
Published Online:13 December 2016
Copyright Holders:Copyright © 2017 Nature
First Published:First published in Pharmacogenomics Journal 18(1):127-135
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record