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Drug-Induced Liver Injury due to Flucloxacillin : Relevance of Multiple Human Leukocyte Antigen Alleles

Nicoletti, Paola (author)
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA;Sema4, Stamford, CT USA
Aithal, Guruprasad P. (author)
Nottingham Univ Hosp NHS Trust, Nottingham Biomed Res Ctr, NIHR, Nottingham, England;Univ Nottingham, Nottingham, England
Chamberlain, Thomas C. (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;Univ British Columbia, Vancouver, BC, Canada
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Coulthard, Sally (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
Alshabeeb, Mohammad (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;King Abdullah Int Med Res Ctr, Dev Med Dept, Riyadh, Saudi Arabia
Grove, Jane, I (author)
Nottingham Univ Hosp NHS Trust, Nottingham Biomed Res Ctr, NIHR, Nottingham, England;Univ Nottingham, Nottingham, England;Univ Nottingham, Nottingham Digest Dis Ctr, Sch Med, Nottingham, England
Andrade, Raul J. (author)
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, UGC Digest, Malaga, Spain;Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain;CIBERehd, Madrid, Spain
Bjornsson, Einar (author)
Natl Univ Hosp Iceland, Dept Internal Med, Div Gastroenterol & Hepatol, Reykjavik, Iceland
Dillon, John F. (author)
Univ Dundee, Ninewells Hosp, Med Res Inst, Dundee, Scotland
Hallberg, Pär, 1974- (author)
Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
Lucena, M. Isabel (author)
Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, UGC Digest, Malaga, Spain;Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain;CIBERehd, Madrid, Spain
Maitland-van der Zee, Anke H. (author)
Univ Amsterdam, AMC, Dept Resp Med, Amsterdam, Netherlands
Martin, Jennifer H. (author)
Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia
Molokhia, Mariam (author)
Kings Coll London, Fac Life Sci & Med, Sch Populat Hlth & Environm Sci, London, England
Pirmohamed, Munir (author)
Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England
Wadelius, Mia (author)
Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
Shen, Yufeng (author)
Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA;Columbia Univ, Dept Biomed Informat, New York, NY USA
Nelson, Matthew R. (author)
GSK, Target Sci, King Of Prussia, PA USA
Daly, Ann K. (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
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 (creator_code:org_t)
2019-03-19
2019
English.
In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 106:1, s. 245-253
Related links:
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Some patients prescribed flucloxacillin (similar to 0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA-B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62; P = 2.67 x 10(-97)). HLA-B*57:03 also showed an association (OR = 79.21; P = 1.2 x 10(-6)). Within the HLA-B protein sequence, imputation showed valine(97), common to HLA-B*57:01 and HLA-B*57:03, had the largest effect (OR = 38.1; P = 9.7 x 10(-97)). We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non-HLA signals for any penicillin-related DILI.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

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