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Genome-Wide Associa...
Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations
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- Cismaru, Anca Liliana (författare)
- Univ Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland; Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, Switzerland
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- Rudin, Deborah (författare)
- Univ Basel, Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland; Univ Basel, Dept Biomed, CH-4051 Basel, Switzerland
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- Ibanez, Luisa (författare)
- Autonomous Univ Barcelona, Hosp Univ Vall d'Hebron, Clin Pharmacol Serv, Fundacio Inst Catala Farmacol, Dept Pharmacol Ther, Barcelona 08035, Spain
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- Liakoni, Evangelia (författare)
- Univ Bern, Univ Hosp Bern, Inselspital, Dept Clin Pharmacol & Toxicol, CH-3010 Bern, Switzerland; Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland
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- Bonadies, Nicolas (författare)
- Univ Bern, Dept Hematol, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland; Univ Bern, Cent Hematol Lab, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland
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- Kreutz, Reinhold (författare)
- Charite 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
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- Carvajal, Alfonso (författare)
- Univ Valladolid, Ctr Estudios Seguridad Medicamentos, Valladolid 47005, Spain
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- Lucena, Maria Isabel (författare)
- Univ Malaga, Hosp Univ Virgen de la Victoria, Serv Farmacol Clin, Inst Invest Biomed Malaga, Malaga 29010, Spain
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- Martin, Javier (författare)
- CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
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- Sancho Ponce, Esther (författare)
- Hosp Gen Cataluna, Serv Hematol & Banc Sang, Sant Cugat Del Valles 08190, Spain
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- Molokhia, Mariam (författare)
- Kings Coll London, Dept Populat Hlth Sci, London WC2R 2LS, England
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- Eriksson, Niclas, 1978- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Institutionen för medicinska vetenskaper
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- Krähenbühl, Stephan (författare)
- Univ Basel, Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland
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- Largiadèr, Carlo R. (författare)
- Univ Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland
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- Haschke, Manuel (författare)
- Univ Bern, Univ Hosp Bern, Inselspital, Dept Clin Pharmacol & Toxicol, CH-3010 Bern, Switzerland; Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland
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- Hallberg, Pär, 1974- (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Amstutz, Ursula (författare)
- Univ Bern, Dept Clin Chem, Inselspital, Univ Hosp Bern, CH-3010 Bern, Switzerland
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(creator_code:org_t)
- 2020-10-29
- 2020
- Engelska.
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 11:11
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- drug-induced agranulocytosis
- metamizole
- dipyrone
- genome-wide association study
- pharmacogenetics
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Cismaru, Anca Li ...
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Rudin, Deborah
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Ibanez, Luisa
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Liakoni, Evangel ...
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Bonadies, Nicola ...
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Kreutz, Reinhold
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Carvajal, Alfons ...
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Lucena, Maria Is ...
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Martin, Javier
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Sancho Ponce, Es ...
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Molokhia, Mariam
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Eriksson, Niclas ...
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Krähenbühl, Step ...
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Largiadèr, Carlo ...
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Haschke, Manuel
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Hallberg, Pär, 1 ...
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Wadelius, Mia
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Amstutz, Ursula
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