Genetic basis for idiosyncratic reactions to antiepileptic drugs.
OBJECTIVE
In recent years, there has been an explosion of genetic research in epilepsy, including a search for genetic markers of adverse reactions to antiepileptic drugs. This article will focus on recent findings concerning genetic factors affecting susceptibility to idiosyncratic reactions to antiepileptic drugs.


RESULTS
Recent studies have investigated the role of genetic factors in the development of antiepileptic drug-induced cutaneous reactions, carbamazepine and valproate-induced liver toxicity, vigabatrin-induced visual field defects, and antiepileptic drug-induced teratogenicity. The greatest progress has been an improved definition of the role of human leukocyte antigen-related genes as predictors of the risk of serious antiepileptic drug-induced cutaneous reactions. This has led to the recommendation that patients of Asian ancestry be tested for the HLA-B*1502 allele, in order to identify those at high risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis after administration of carbamazepine and, possibly, phenytoin and other antiepileptic drugs.


CONCLUSIONS
Future research will probably lead to discovery of additional genetic predictors of susceptibility to adverse reactions to antiepileptic drugs. Identification of genetic markers should, in turn, allow unravelling of the molecular mechanisms underlying these reactions. Ultimately, these advances should lead not only to improved personalization of therapy but also to development of safer drugs.
Franciotta
Diego
D
Foundation Neurological Institute C. Mondino, IRCCS, Pavia, Italy.
Kwan
Patrick
P
Perucca
Emilio
E
D000927:Anticonvulsants / Q000009:adverse effects* / Q000276:immunology; D002220:Carbamazepine / Q000009:adverse effects / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D004827:Epilepsy / Q000188:drug therapy*; D005982:Glutathione Transferase / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D013262:Stevens-Johnson Syndrome / Q000276:immunology; D013723:Teratogens; D014635:Valproic Acid / Q000009:adverse effects / Q000276:immunology; D020888:Vigabatrin / Q000009:adverse effects / Q000494:pharmacology; D014794:Visual Fields / Q000187:drug effects
D000927:Anticonvulsants; D015235:HLA-B Antigens; D013723:Teratogens; D002220:Carbamazepine; D014635:Valproic Acid; D005982:Glutathione Transferase; D020888:Vigabatrin