Genetic association studies in drug-induced liver injury.
Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.
Daly
Ann K
AK
Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, United Kingdom.
Day
Chris P
CP
D016907:Adverse Drug Reaction Reporting Systems; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000995:Antitubercular Agents / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D004008:Diclofenac / Q000009:adverse effects; D005436:Floxacillin / Q000009:adverse effects; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000995:Antitubercular Agents; D015235:HLA-B Antigens; C484830:HLA-B*57:01 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D004008:Diclofenac; D005436:Floxacillin; D019980:Amoxicillin-Potassium Clavulanate Combination; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human