A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury.

Nature Genetics
Jonathan B SingerCharles A Paulding

Abstract

Lumiracoxib is a selective cyclooxygenase-2 inhibitor developed for the symptomatic treatment of osteoarthritis and acute pain. Concerns over hepatotoxicity have contributed to the withdrawal or non-approval of lumiracoxib in most major drug markets worldwide. We performed a case-control genome-wide association study on 41 lumiracoxib-treated patients with liver injury (cases) and 176 matched lumiracoxib-treated patients without liver injury (controls). Several SNPs from the MHC class II region showed strong evidence of association (the top SNP was rs9270986 with P = 2.8 x 10(-10)). These findings were replicated in an independent set of 98 lumiracoxib-treated cases and 405 matched lumiracoxib-treated controls (top SNP rs3129900, P = 4.4 x 10(-12)). Fine mapping identified a strong association to a common HLA haplotype (HLA-DRB1*1501-HLA-DQB1*0602-HLA-DRB5*0101-HLA-DQA1*0102, most significant allele P = 6.8 x 10(-25), allelic odds ratio = 5.0, 95% CI 3.6-7.0). These results offer the potential to improve the safety profile of lumiracoxib by identifying individuals at elevated risk for liver injury and excluding them from lumiracoxib treatment.

References

Aug 26, 1998·The American Journal of Cardiology·W R Daley
Oct 27, 1999·Gastroenterology·M L HautekeeteA P Geubel
Apr 12, 2002·Lancet·Seth HetheringtonAllen D Roses
Apr 2, 2004·Nature·Wen-Hung ChungYuan-Tsong Chen
Jun 3, 2005·Nature Reviews. Drug Discovery·Neil Kaplowitz
Feb 17, 2006·The New England Journal of Medicine·Victor J Navarro, John R Senior
Mar 23, 2006·Pharmacoepidemiology and Drug Safety·Robert Temple
Aug 2, 2006·Annual Review of Pharmacology and Toxicology·Jack Uetrecht
Nov 1, 2006·Allergology International : Official Journal of the Japanese Society of Allergology·Werner J PichlerBasil Gerber
Jul 31, 2007·Expert Opinion on Pharmacotherapy·Bernard Bannwarth, Francis Bérenbaum
Aug 29, 2007·Clinics in Liver Disease·John R Senior
Feb 8, 2008·The New England Journal of Medicine·Simon MallalUNKNOWN PREDICT-1 Study Team
Jun 11, 2008·Nature Reviews. Genetics·Jorge R OksenbergStephen L Hauser
Jun 2, 2009·Nature Genetics·Ann K DalyUNKNOWN International SAE Consortium

❮ Previous
Next ❯

Citations

Jun 27, 2012·European Journal of Clinical Pharmacology·Isla S MackenzieThomas M Macdonald
May 25, 2011·Clinical Rheumatology·Thomas J SchnitzerThomas Maxwell
Nov 13, 2013·Medicina clínica·Ana M Peiró Peiró
Jun 3, 2011·Chemical Research in Toxicology·Alexander Kamb
May 3, 2013·Journal of Human Genetics·Nahoko Kaniwa, Yoshiro Saito
Nov 10, 2012·Nature Biotechnology·Andrew R Harper, Eric J Topol
Mar 15, 2011·Nature Genetics·Ali G GharaviRichard P Lifton
Dec 1, 2010·Nature Reviews. Genetics·Russ B AltmanDan Roden
Nov 4, 2010·Nature Reviews. Gastroenterology & Hepatology·Marcin KrawczykFrank Lammert
Mar 10, 2011·Nature Reviews. Gastroenterology & Hepatology·Shannan Tujios, Robert J Fontana
Jan 26, 2011·Nature Reviews. Rheumatology·Guruprasad P Aithal
Oct 10, 2012·The Pharmacogenomics Journal·J E WyattS Harirforoosh
Aug 22, 2012·Human Molecular Genetics·Chun-Yu WeiYuan-Tsong Chen
Dec 15, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Inger Johansson, Magnus Ingelman-Sundberg
Mar 29, 2012·Pharmacogenetics and Genomics·Masayuki AokiMichiaki Kubo
Sep 13, 2012·Pharmacogenetics and Genomics·Thomas J UrbanUNKNOWN International Serious Adverse Events Consortium
May 25, 2012·Journal of Gastroenterology and Hepatology·Shivakumar Chitturi, Geoffrey C Farrell
Mar 12, 2013·Pharmacological Reviews·Jack Uetrecht, Dean J Naisbitt
Sep 29, 2012·Science Translational Medicine·Kathleen M GiacominiYusuke Nakamura
Jan 31, 2013·Genome Medicine·Ann K Daly
Jan 5, 2012·Drug Metabolism and Pharmacokinetics·Shyh-Yuh LiouMasashi Hirayama
Nov 2, 2011·Drug Metabolism and Pharmacokinetics·Chun-Yu WeiYuan-Tsong Chen
Dec 15, 2010·Pharmacogenomics·Lois M HinmanWilliam Pignato
Nov 29, 2011·Pharmacogenomics·Andrew KasarskisEric Schadt
Aug 28, 2012·Pharmacogenomics·Rebecca PavlosElizabeth Phillips
Jan 17, 2014·Current Allergy and Asthma Reports·Eric Karlin, Elizabeth Phillips
Nov 22, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Haydeh Payami, Stewart A Factor
May 28, 2013·International Journal of Endocrinology·Gilles WilleminKaori Minehira
Oct 18, 2012·Annual Review of Medicine·Krzysztof KirylukAli G Gharavi
Oct 18, 2012·Annual Review of Pharmacology and Toxicology·Kaixin Zhou, Ewan R Pearson
Aug 9, 2011·Annual Review of Pharmacology and Toxicology·Ann K Daly
Jun 6, 2014·Annual Review of Genomics and Human Genetics·Munir Pirmohamed
Apr 16, 2014·BioMed Research International·Shih-Chi SuShuen-Iu Hung
Feb 26, 2014·The Journal of Allergy and Clinical Immunology. in Practice·Rebecca PavlosElizabeth Phillips
Oct 30, 2014·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Paul B WatkinsJohn R Senior
Oct 30, 2014·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Arie RegevPaul B Watkins
Feb 9, 2013·Genes and Immunity·S J HebbringM H Brilliant
Jan 1, 2012·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Maurizio CardelliMauro Provinciali
Jun 5, 2013·Current Hepatitis Reports·Thanh Tran, William M Lee

❮ Previous
Next ❯

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