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  • Nicoletti, PaolaIcahn Sch Med Mt Sinai, New York, NY 10029 USA;Sema4, Stamford, CT USA (author)

Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-07-03
  • John Wiley & Sons,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-396697
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396697URI
  • https://doi.org/10.1002/cpt.1493DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 x 10(-9)) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 x 10(-9)) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.

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  • Barrett, SarahUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • McEvoy, LaurenceUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • Daly, Ann K.Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England (author)
  • Aithal, GuruprasadNottingham Univ Hosp NHS Trust, Nottingham Biomed Res Unit, NIHR, Nottingham, England;Univ Nottingham, Nottingham, England (author)
  • Isabel Lucena, M.Univ Malaga, UGC Digest, Clin Pharmacol Serv, Inst Invest Biomed Malaga IBIMA,Hosp Univ Virgen, Malaga, Spain;Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain (author)
  • Andrade, Raul J.Univ Malaga, UGC Digest, Clin Pharmacol Serv, Inst Invest Biomed Malaga IBIMA,Hosp Univ Virgen, Malaga, Spain;Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain (author)
  • Wadelius, MiaUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel (author)
  • Hallberg, Pär,1974-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk farmakogenomik och osteoporos(Swepub:uu)pahal677 (author)
  • Stephens, CamillaUniv Malaga, UGC Digest, Clin Pharmacol Serv, Inst Invest Biomed Malaga IBIMA,Hosp Univ Virgen, Malaga, Spain;Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain (author)
  • Bjornsson, Einar S.Landspitali Univ Hosp, Dept Internal Med, Reykjavik, Iceland (author)
  • Friedmann, PeterUniv Southampton, Sch Med, Dermatol Unit, Southampton, Hants, England (author)
  • Kainu, KatiUniv Helsinki, Cent Hosp, Clin Res Unit Pulm Dis, Helsinki, Finland (author)
  • Laitinen, TarjaUniv Helsinki, Cent Hosp, Clin Res Unit Pulm Dis, Helsinki, Finland (author)
  • Marson, AnthonyUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • Molokhia, MariamKings Coll London, Sch Populat Sci & Hlth Serv Res, London, England (author)
  • Phillips, ElizabethVanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA (author)
  • Pichler, WernerADR AC GmbH, Bern, Switzerland (author)
  • Romano, AntoninoComplesso Integrato Columbus, Allergy Unit, Rome, Italy (author)
  • Shear, NeilUniv Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada (author)
  • Sills, GraemeUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • Tanno, Luciana K.Hosp Sirio Libanes, Sao Paulo, Brazil (author)
  • Swale, AshleyColumbia Univ, Dept Syst Biol, New York, NY USA (author)
  • Floratos, ArisColumbia Univ, Dept Syst Biol, New York, NY USA (author)
  • Shen, YufengColumbia Univ, Dept Syst Biol, New York, NY USA (author)
  • Nelson, Matthew R.GSK, Target Sci, King Of Prussia, PA USA (author)
  • Watkins, Paul B.Univ N Carolina, Eshelman Sch Pharm, Inst Drug Safety Sci, Chapel Hill, NC 27515 USA (author)
  • Daly, Mark J.Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02115 USA (author)
  • Morris, Andrew P.Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England (author)
  • Alfirevic, AnaUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • Pirmohamed, MunirUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (author)
  • Icahn Sch Med Mt Sinai, New York, NY 10029 USA;Sema4, Stamford, CT USAUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England (creator_code:org_t)

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  • In:Clinical Pharmacology and Therapeutics: John Wiley & Sons106:5, s. 1028-10360009-92361532-6535

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