Pharmacogenetics of hypersensitivity drug reactions.
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions.
Department of internal medicine, clinical immunology unit, centre of excellence for biomedical research, university of Genoa, 16132 Genoa, Italy. Electronic address: negrini@unige.it.
Simone
S
Negrini
Pharmacology department, faculty of medicine Paris-Sud, UMR 1184, CEA, DSV/iMETI, division of immuno-virology, IDMIT, Inserm center for immunology of viral infections and autoimmune diseases, hôpital Bicêtre, university Paris Sud, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
Laurent
L
Becquemont
D000493:Allopurinol / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D010597:Pharmacogenetics; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D000099227:Abacavir
D000493:Allopurinol; D000927:Anticonvulsants; D002220:Carbamazepine; D015224:Dideoxynucleosides; D004791:Enzyme Inhibitors; D006680:HLA Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir
Abacavir; Allopurinol; Carbamazepine; HLA; Hypersensitivity drug reactions