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A Missense Variant ...
A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury
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- Cirulli, Elizabeth T. (författare)
- Duke Univ, Duke Ctr Appl Genom & Precis Med, Durham, NC USA
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- Nicoletti, Paola (författare)
- Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, One Gustave Levy Pl, New York, NY 10029 USA;Sema4, Stamford, CT USA
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- Abramson, Karen (författare)
- Duke Univ, Duke Mol Physiol Inst, Durham, NC USA
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- Andrade, Raul J. (författare)
- Univ Malaga, Hosp Univ Virgen de la Victoria, Ctr Invest Biomed Red Enfermedades Hepat & Digest, UGC Digest,Inst Invest Biomed Malaga IBIMA, Malaga, Spain;Univ Malaga, IBIMA Hosp Univ Virgen de la Victoria, Malaga, Spain;CIBERehd, Madrid, Spain
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- Bjornsson, Einar S. (författare)
- Landspitali Univ Hosp, Dept Internal Med, Reykjavik, Iceland
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- Chalasani, Naga (författare)
- Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA
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- Fontana, Robert J. (författare)
- Univ Michigan, Ann Arbor, MI 48109 USA
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- Hallberg, Pär, 1974- (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Li, Yi Ju (författare)
- Duke Univ, Duke Mol Physiol Inst, Durham, NC USA;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA
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- Lucena, M. Isabel (författare)
- Univ Malaga, Hosp Univ Virgen de la Victoria, Ctr Invest Biomed Red Enfermedades Hepat & Digest, UGC Digest,Inst Invest Biomed Malaga IBIMA, Malaga, Spain;Univ Malaga, IBIMA Hosp Univ Virgen de la Victoria, Malaga, Spain;CIBERehd, Madrid, Spain
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- Long, Nanye (författare)
- Michigan State Univ, Inst Cyber Enabled Res, E Lansing, MI 48824 USA
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- Molokhia, Mariam (författare)
- Kings Coll London, Sch Populat Hlth & Environm Sci, London, England;Kings Coll London, London, England
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- Nelson, Matthew R. (författare)
- GSK, Target Sci, King Of Prussia, PA USA
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- Odin, Joseph A. (författare)
- Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
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- Pirmohamed, Munir (författare)
- Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England
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- Rafnar, Thorunn (författare)
- deCODE Genet, IS-101 Reykjavik, Iceland
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- Serrano, Jose (författare)
- NIDDK, Bethesda, MD 20892 USA
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- Stefansson, Kari (författare)
- deCODE Genet, IS-101 Reykjavik, Iceland
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- Stolz, Andrew (författare)
- Univ Southern Calif, Los Angeles, CA USA
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- Daly, Ann K. (författare)
- Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
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- Aithal, Guruprasad P. (författare)
- Nottingham Univ Hosp NHS Trust, Nottingham Digest Dis Ctr, Nottingham, England;Nottingham Univ Hosp NHS Trust, Natl Inst Hlth Res, Nottingham Biomed Res Ctr, Nottingham, England;Univ Nottingham, Nottingham, England;Nottingham Univ Hosp NHS Trust, Nottingham Digest Dis Biomed Res Unit, Natl Inst Hlth Res, Nottingham, England
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- Watkins, Paul B. (författare)
- Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC 27515 USA;Univ N Carolina, Inst Drug Safety Sci, Res Triangle Pk, NC USA
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- Bessone, Fernando (författare)
- Univ Nacl Rosario, Rosario, Santa Fe, Argentina
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- Bjornsson, Einar (författare)
- Natl Univ Hosp Iceland, Dept Internal Med, Div Gastroenterol & Hepatol, Reykjavik, Iceland
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- Cascorbi, Ingolf (författare)
- Univ Hosp Schleswig Holstein, Inst Expt & Clin Pharmacol, Kiel, Germany
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- Dillon, John F. (författare)
- Ninewells Hosp & Med Sch, Dundee, Scotland
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- Day, Christopher P. (författare)
- Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
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- Hernandez, Nelia (författare)
- Univ Republica, Montevideo, Uruguay
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- Ibanez, Luisa (författare)
- Hosp Univ Vall dHebron, Barcelona, Spain
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- Kullak-Ublic, Gerd A. (författare)
- Univ Zurich, Zurich, Switzerland
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- Laitinen, Tarja (författare)
- Univ Helsinki, Cent Hosp, Helsinki, Finland
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- Larrey, Dominique (författare)
- Hop St Eloi, Montpellier, France
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- Maitland-van der Zee, Anke (författare)
- AMC, Amsterdam, Netherlands
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- Martin, Jennifer H. (författare)
- Univ Newcastle, Newcastle, NSW, Australia
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- Menzies, Dick (författare)
- MUHC, Montreal, PQ, Canada;McGill Univ, Montreal Chest Inst, Montreal, PQ, Canada
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- Qin, Shengying (författare)
- Shanghai Jiao Tong Univ, Shanghai, Peoples R China
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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(creator_code:org_t)
- W B SAUNDERS CO-ELSEVIER INC, 2019
- 2019
- Engelska.
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 156:6, s. 1707-1716
- Relaterad länk:
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https://helda.helsin...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings.RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01.CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- Amino Acid Change
- GWAS
- Mutation
- Inflammation
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- ref (ämneskategori)
- art (ämneskategori)
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Cirulli, Elizabe ...
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Nicoletti, Paola
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Abramson, Karen
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Andrade, Raul J.
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Bjornsson, Einar ...
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Chalasani, Naga
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visa fler...
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Fontana, Robert ...
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Hallberg, Pär, 1 ...
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Li, Yi Ju
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Lucena, M. Isabe ...
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Long, Nanye
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Molokhia, Mariam
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Nelson, Matthew ...
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Odin, Joseph A.
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Pirmohamed, Muni ...
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Rafnar, Thorunn
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Serrano, Jose
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Stefansson, Kari
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Stolz, Andrew
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Daly, Ann K.
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Aithal, Gurupras ...
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Watkins, Paul B.
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Bessone, Fernand ...
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Bjornsson, Einar
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Cascorbi, Ingolf
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Dillon, John F.
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Day, Christopher ...
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Hernandez, Nelia
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Ibanez, Luisa
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Kullak-Ublic, Ge ...
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Laitinen, Tarja
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Larrey, Dominiqu ...
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Maitland-van der ...
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Martin, Jennifer ...
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Menzies, Dick
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Qin, Shengying
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Wadelius, Mia
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Gastroenterology
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Uppsala universitet