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

Publication ,  Journal Article
Floyd, JS; Sitlani, CM; Avery, CL; Noordam, R; Li, X; Smith, AV; Gogarten, SM; Li, J; Broer, L; Evans, DS; Trompet, S; Brody, JA; Stewart, JD ...
Published in: Pharmacogenomics J
January 2018

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.

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Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

January 2018

Volume

18

Issue

1

Start / End Page

127 / 135

Location

United States

Related Subject Headings

  • Sulfonylurea Compounds
  • Pharmacology & Pharmacy
  • Pharmacogenomic Testing
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Female
 

Citation

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Floyd, J. S., Sitlani, C. M., Avery, C. L., Noordam, R., Li, X., Smith, A. V., … Stricker, B. H. (2018). Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics J, 18(1), 127–135. https://doi.org/10.1038/tpj.2016.90
Floyd, J. S., C. M. Sitlani, C. L. Avery, R. Noordam, X. Li, A. V. Smith, S. M. Gogarten, et al. “Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.Pharmacogenomics J 18, no. 1 (January 2018): 127–35. https://doi.org/10.1038/tpj.2016.90.
Floyd JS, Sitlani CM, Avery CL, Noordam R, Li X, Smith AV, et al. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics J. 2018 Jan;18(1):127–35.
Floyd, J. S., et al. “Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.Pharmacogenomics J, vol. 18, no. 1, Jan. 2018, pp. 127–35. Pubmed, doi:10.1038/tpj.2016.90.
Floyd JS, Sitlani CM, Avery CL, Noordam R, Li X, Smith AV, Gogarten SM, Li J, Broer L, Evans DS, Trompet S, Brody JA, Stewart JD, Eicher JD, Seyerle AA, Roach J, Lange LA, Lin HJ, Kors JA, Harris TB, Li-Gao R, Sattar N, Cummings SR, Wiggins KL, Napier MD, Stürmer T, Bis JC, Kerr KF, Uitterlinden AG, Taylor KD, Stott DJ, de Mutsert R, Launer LJ, Busch EL, Méndez-Giráldez R, Sotoodehnia N, Soliman EZ, Li Y, Duan Q, Rosendaal FR, Slagboom PE, Wilhelmsen KC, Reiner AP, Chen Y-D, Heckbert SR, Kaplan RC, Rice KM, Jukema JW, Johnson AD, Liu Y, Mook-Kanamori DO, Gudnason V, Wilson JG, Rotter JI, Laurie CC, Psaty BM, Whitsel EA, Cupples LA, Stricker BH. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics J. 2018 Jan;18(1):127–135.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

January 2018

Volume

18

Issue

1

Start / End Page

127 / 135

Location

United States

Related Subject Headings

  • Sulfonylurea Compounds
  • Pharmacology & Pharmacy
  • Pharmacogenomic Testing
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Female