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Sökning: (WFRF:(Laitinen Tarja)) mspu:(article) > (2017) > Association of Live...

  • Nicoletti, PaolaColumbia Univ, Dept Syst Biol, New York, NY USA. (författare)

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • W B SAUNDERS CO-ELSEVIER INC,2017
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-320025
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320025URI
  • https://doi.org/10.1053/j.gastro.2016.12.016DOI

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  • Språk:engelska
  • Sammanfattning på:engelska

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

Anmärkningar

  • BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for druginduced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A* 33: 01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9 - 3.8; P = 2.4 x 10(-8)) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6 - 2.5; P = 9.7 x 10(-9)). The association with A* 33: 01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A* 33: 01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6 - 2.7; P = 4.8 x 10(-9)). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0 - 9.5; P = 7.1 x 10(-9)). We validated the association between A* 33: 01 terbinafine-and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A* 33: 01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.

Ämnesord och genrebeteckningar

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

  • Aithal, Guruprasad P.Natl Hlth Serv Trust, Univ Nottingham Hosp, Natl Inst Hlth Res, Nottingham Digest Dis Biomed Res Unit, Nottingham, England.;Univ Nottingham, Nottingham, England. (författare)
  • Bjornsson, Einar S.Landspitali Univ Hosp, Dept Internal Med, Reykjavik, Iceland. (författare)
  • Andrade, Raul J.Univ Malaga, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Hosp Univ Virgen Victoria, Unidad Gest Clin Digest,Inst Invest Biomed Malaga, Malaga, Spain. (författare)
  • Sawle, AshleyColumbia Univ, Dept Syst Biol, New York, NY USA. (författare)
  • Arrese, MarcoPontificia Univ Catolica Chile, Dept Gastroenterol, Escuela Med, Santiago, Chile. (författare)
  • Barnhart, Huiman X.Duke Univ, Durham, NC USA. (författare)
  • Bondon-Guitton, EmmanuelleUniv Toulouse, Toulouse, France. (författare)
  • Hayashi, Paul H.Univ North Carolina Chapel Hill, Dept Internal Med, Chapel Hill, NC USA. (författare)
  • Bessone, FernandoUniv Nacl Rosario, Serv Gastroenterol & Hepatol, Rosario, Santa Fe, Argentina. (författare)
  • Carvajal, AlfonsoUniv Valladolid, Valladolid, Spain. (författare)
  • Cascorbi, IngolfUniv Hosp Schleswig Holstein, Inst Expt & Clin Pharmacol, Kiel, Germany. (författare)
  • Cirulli, Elizabeth T.Duke Univ, Durham, NC USA. (författare)
  • Chalasani, NagaIndiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. (författare)
  • Conforti, AnitaUniv Hosp, Verona, Italy. (författare)
  • Coulthard, Sally A.Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. (författare)
  • Daly, Mark J.Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA USA. (författare)
  • Day, Christopher P.Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. (författare)
  • Dillon, John F.Univ Dundee, Res Inst, Ninewells Hosp, Dundee, Scotland. (författare)
  • Fontana, Robert J.Univ Michigan, Ann Arbor, MI 48109 USA. (författare)
  • Grove, Jane I.Natl Hlth Serv Trust, Univ Nottingham Hosp, Natl Inst Hlth Res, Nottingham Digest Dis Biomed Res Unit, Nottingham, England.;Univ Nottingham, Nottingham, England. (författare)
  • Hallberg, Pär,1974-Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab(Swepub:uu)pahal677 (författare)
  • Hernandez, NeliaUniv Republica, Fac Med, Montevideo, Uruguay. (författare)
  • Ibanez, LuisaUniv Autonoma Barcelona, Fundacio Inst Catala Farmacol, Hosp Univ Vall dHebron, Barcelona, Spain. (författare)
  • Kullak-Ublick, Gerd A.Univ Hosp, Dept Clin Pharmacol & Toxicol, Zurich, Switzerland.;Univ Zurich, Zurich, Switzerland. (författare)
  • Laitinen, TarjaUniv Helsinki, Cent Hosp, Clin Res Unit Pulm Dis, Helsinki, Finland. (författare)
  • Larrey, DominiqueSt Eloi Hosp, Liver Unit, Ctr Hosp Univ, Montpellier, France. (författare)
  • Lucena, M. IsabelUniv Malaga, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Hosp Univ Virgen Victoria, Unidad Gest Clin Digest,Inst Invest Biomed Malaga, Malaga, Spain. (författare)
  • Maitland-van der Zee, Anke H.Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands. (författare)
  • Martin, Jennifer H.Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. (författare)
  • Molokhia, MariamKings Coll London, Dept Primary Care & Publ Hlth Sci, London, England. (författare)
  • Pirmohamed, MunirUniv Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England. (författare)
  • Powell, Elizabeth E.Univ Queensland, Sch Med, Ctr Liver Dis Res, Brisbane, Qld, Australia. (författare)
  • Qin, ShengyingShanghai Jiao Tong Univ, BioX Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai, Peoples R China. (författare)
  • Serrano, JoseNatl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. Univ Southern Calif, Los Angeles, CA USA. (författare)
  • Stephens, CamillaUniv Malaga, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Hosp Univ Virgen Victoria, Unidad Gest Clin Digest,Inst Invest Biomed Malaga, Malaga, Spain. (författare)
  • Stolz, Andrew (författare)
  • Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)miawadel (författare)
  • Watkins, Paul B.Univ N Carolina, Inst Drug Safety Sci, Eshelman Sch Pharm, Chapel Hill, NC USA. (författare)
  • Floratos, ArisColumbia Univ, Dept Syst Biol, New York, NY USA. (författare)
  • Shen, YufengColumbia Univ, Dept Syst Biol, New York, NY USA. (författare)
  • Nelson, Matthew R.GlaxoSmithKlein, Target Sci, King Of Prussia, PA USA. (författare)
  • Urban, Thomas J.Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. (författare)
  • Daly, Ann K.Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. (författare)
  • Columbia Univ, Dept Syst Biol, New York, NY USA.Natl Hlth Serv Trust, Univ Nottingham Hosp, Natl Inst Hlth Res, Nottingham Digest Dis Biomed Res Unit, Nottingham, England.;Univ Nottingham, Nottingham, England. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Gastroenterology: W B SAUNDERS CO-ELSEVIER INC152:5, s. 1078-10890016-50851528-0012

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