RGD Reference Report - A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

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

Authors: Singer, Jonathan B  Lewitzky, Steve  Leroy, Elisabeth  Yang, Fan  Zhao, Xiaojun  Klickstein, Lloyd  Wright, Timothy M  Meyer, Joanne  Paulding, Charles A 
Citation: Singer JB, etal., Nat Genet. 2010 Aug;42(8):711-4. doi: 10.1038/ng.632. Epub 2010 Jul 18.
RGD ID: 14398844
Pubmed: PMID:20639878   (View Abstract at PubMed)
DOI: DOI:10.1038/ng.632   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H2-AaMouseChemical and Drug Induced Liver Injury susceptibilityISOHLA-DQA1 (Homo sapiens)DNA:polymorphism: :HLA-DQA1*0102(human)RGD 
HLA-DQA1HumanChemical and Drug Induced Liver Injury susceptibilityIAGP DNA:polymorphism: :HLA-DQA1*0102(human)RGD 
RT1-BaRatChemical and Drug Induced Liver Injury susceptibilityISOHLA-DQA1 (Homo sapiens)DNA:polymorphism: :HLA-DQA1*0102(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Ba  (RT1 class II, locus Ba)

Genes (Mus musculus)
H2-Aa  (histocompatibility 2, class II antigen A, alpha)

Genes (Homo sapiens)
HLA-DQA1  (major histocompatibility complex, class II, DQ alpha 1)


Additional Information