title: Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury.
abstract: Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.
authors: Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
authors: Nahoko
authors: N
authors: Kaniwa
authors: Yoshiro
authors: Y
authors: Saito
mesh_terms: D000483:Alleles; D000493:Allopurinol / Q000009:adverse effects; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects; D001384:Azetidines / Q000009:adverse effects; D001596:Benzylamines / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000276:immunology*; D004008:Diclofenac / Q000009:adverse effects / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005436:Floxacillin / Q000009:adverse effects; D005819:Genetic Markers; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D059848:HLA-DQ alpha-Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D000077341:Lapatinib; D010597:Pharmacogenetics; D011799:Quinazolines / Q000009:adverse effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000235:genetics / Q000276:immunology; D013988:Ticlopidine / Q000009:adverse effects; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D019980:Amoxicillin-Potassium Clavulanate Combination; D001384:Azetidines; D001596:Benzylamines; D002220:Carbamazepine; D004008:Diclofenac; D015224:Dideoxynucleosides; D005436:Floxacillin; D005819:Genetic Markers; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059848:HLA-DQ alpha-Chains; D000077341:Lapatinib; D011799:Quinazolines; D013988:Ticlopidine; D000099227:Abacavir; C069527:HLA-A31 antigen; C103707:HLA-B57 antigen; C069050:HLA-DQA1 antigen; C426686:ximelagatran; C473384:lumiracoxib