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  • Cismaru, Anca LilianaUniv Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland; Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, Switzerland (författare)

Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • 2020-10-29
  • MDPI AG,2020
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-428983
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-428983URI
  • https://doi.org/10.3390/genes11111275DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10−7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41–6.68, p = 1.01 × 10−7) and rs4427239 (OR = 5.47, 95%CI: 2.81–10.65, p = 5.75 × 10−7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Rudin, DeborahUniv Basel, Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland; Univ Basel, Dept Biomed, CH-4051 Basel, Switzerland (författare)
  • Ibanez, LuisaAutonomous Univ Barcelona, Hosp Univ Vall d'Hebron, Clin Pharmacol Serv, Fundacio Inst Catala Farmacol, Dept Pharmacol Ther, Barcelona 08035, Spain (författare)
  • Liakoni, EvangeliaUniv Bern, Univ Hosp Bern, Inselspital, Dept Clin Pharmacol & Toxicol, CH-3010 Bern, Switzerland; Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland (författare)
  • Bonadies, NicolasUniv Bern, Dept Hematol, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland; Univ Bern, Cent Hematol Lab, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland (författare)
  • Kreutz, ReinholdCharite Univ Med Berlin, D-10117 Berlin, Germany; Free Univ Berlin, D-10117 Berlin, Germany; Humboldt Univ, D-10117 Berlin, Germany; Berlin Inst Hlth, Inst Klin Pharmakol & Toxikol, D-10117 Berlin, Germany (författare)
  • Carvajal, AlfonsoUniv Valladolid, Ctr Estudios Seguridad Medicamentos, Valladolid 47005, Spain (författare)
  • Lucena, Maria IsabelUniv Malaga, Hosp Univ Virgen de la Victoria, Serv Farmacol Clin, Inst Invest Biomed Malaga, Malaga 29010, Spain (författare)
  • Martin, JavierCSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain (författare)
  • Sancho Ponce, EstherHosp Gen Cataluna, Serv Hematol & Banc Sang, Sant Cugat Del Valles 08190, Spain (författare)
  • Molokhia, MariamKings Coll London, Dept Populat Hlth Sci, London WC2R 2LS, England (författare)
  • Eriksson, Niclas,1978-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Institutionen för medicinska vetenskaper(Swepub:uu)nieri103 (författare)
  • Krähenbühl, StephanUniv Basel, Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland (författare)
  • Largiadèr, Carlo R.Univ Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland (författare)
  • Haschke, ManuelUniv Bern, Univ Hosp Bern, Inselspital, Dept Clin Pharmacol & Toxicol, CH-3010 Bern, Switzerland; Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland (författare)
  • Hallberg, Pär,1974-Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)pahal677 (författare)
  • Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)miawadel (författare)
  • Amstutz, UrsulaUniv Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland (författare)
  • Univ Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland; Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, SwitzerlandUniv Basel, Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland; Univ Basel, Dept Biomed, CH-4051 Basel, Switzerland (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Genes: MDPI AG11:112073-4425

Internetlänk

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  • Genes (Sök värdpublikationen i LIBRIS)

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