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Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.
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-Di; Heckbert, S R; Kaplan, R C; Rice, K M; Jukema, J W; Johnson, A D; Liu, Y.
Affiliation
  • Floyd JS; Deparments of Epidemiology and Medicine, University of Washington, Seattle, WA, USA.
  • Sitlani CM; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Avery CL; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Noordam R; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Li X; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Smith AV; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Gogarten SM; Icelandic Heart Association, Kopavogur, Iceland.
  • Li J; Faculty of Medicine, University of Iceland, Reykavik, Iceland.
  • Broer L; Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Evans DS; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
  • Trompet S; Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Brody JA; California Pacific Medical Center Research Institute, San Francisco, CA, USA.
  • Stewart JD; Department of Cardiology and Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Eicher JD; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Seyerle AA; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Roach J; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
  • Lange LA; Population Sciences Branch, National Heart Lung and Blood Institute, National Institutes of Health, Framingham, MA, USA.
  • Lin HJ; The Framingham Heart Study, Framingham, MA, USA.
  • Kors JA; Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
  • Harris TB; Research Computing Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Li-Gao R; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Sattar N; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Cummings SR; Division of Medical Genetics, Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Wiggins KL; Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Napier MD; Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA.
  • Stürmer T; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Bis JC; BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
  • Kerr KF; California Pacific Medical Center Research Institute, San Francisco, CA, USA.
  • Uitterlinden AG; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Taylor KD; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Stott DJ; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • de Mutsert R; Center for Pharmacoepidemiology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Launer LJ; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Busch EL; Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Méndez-Giráldez R; Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Sotoodehnia N; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Soliman EZ; Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Scotland, UK.
  • Li Y; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Duan Q; Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA.
  • Rosendaal FR; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Slagboom PE; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Wilhelmsen KC; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Reiner AP; Deparments of Epidemiology and Medicine, University of Washington, Seattle, WA, USA.
  • Chen YD; Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Heckbert SR; Department of Biostatistics, Computer Science, and Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Kaplan RC; Research Computing Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Rice KM; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Jukema JW; Department of Medical Statistics and Bioinformatics, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Johnson AD; Research Computing Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Liu Y; The Renaissance Computing Institute, Chapel Hill, NC, USA.
Pharmacogenomics J ; 18(1): 127-135, 2018 01.
Article in En | MEDLINE | ID: mdl-27958378
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.
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Full text: 1 Database: MEDLINE Main subject: Sulfonylurea Compounds / Ethnicity / Electrocardiography Type of study: Systematic_reviews Limits: Aged / Female / Humans / Male / Middle aged Language: En Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Sulfonylurea Compounds / Ethnicity / Electrocardiography Type of study: Systematic_reviews Limits: Aged / Female / Humans / Male / Middle aged Language: En Year: 2018 Type: Article