title: Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response.
abstract: Carbamazepine (CBZ) is a first-line widely used anticonvulsant. It has a narrow therapeutic index and exhibits considerable interindividual and interethnic variability in clinical efficacy and adverse drug reactions including potentially life-threatening hypersensitivity reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The most important pharmacogenetic finding is related to the association of CBZ-induced hypersensitivity with human leukocyte antigens (HLA class I and II alleles). Moreover, genotyping for HLA-B*15:02 allele is required prior to initiating CBZ in Asians and Asian ancestry patients, demonstrating the usefulness of biomarkers to avoid adverse drug reactions. On the other hand, in order to explain the differences in the clinical response to CBZ, genetic polymorphisms in phase I (CYP3A4, CYP3A5 and EPHX1) and phase II (UGT2B7) metabolising enzymes have been assessed; additionally, the influence of transporters (ABCB1 and ABCC2), receptors (PXR) and other drug targets (voltage- gated Na+ channels) in CBZ clinical response has been evaluated. To date, these studies are controversial and require further investigations to clarify the functional role of these polymorphisms as potential biomarkers in regard to CBZ therapy.
authors.forename: Nancy Monroy
authors.initials: NM
authors.lastname: Jaramillo
authors.forename: Ingrid Fricke
authors.initials: IF
authors.lastname: Galindo
authors.forename: Alberto Ortega
authors.initials: AO
authors.lastname: Vázquez
authors.forename: Helgi Jung
authors.initials: HJ
authors.lastname: Cook
authors.forename: Adrián
authors.initials: A
authors.lastname: LLerena
authors.forename: Marisol López
authors.initials: ML
authors.lastname: López
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000009:adverse effects* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000276:immunology; D005819:Genetic Markers / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D010597:Pharmacogenetics
chemical_list: C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000927:Anticonvulsants; D005819:Genetic Markers; D015395:Histocompatibility Antigens Class I; D000089762:Multidrug Resistance-Associated Protein 2; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System