title: Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.
abstract: OBJECTIVE
  An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.
  
  
  METHODS
  We recruited patients with lamotrigine-induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958 British birth cohort was used as a control (n = 1296). HLA-A*3101 was imputed from genome-wide association study data. We applied genome-wide association to study lamotrigine- and phenytoin-induced cADR, and total cADR cases combined.
  
  
  RESULTS
  Neither HLA-A*3101 nor any other genetic marker significantly predicted lamotrigine- or phenytoin-induced cADRs.
  
  
  CONCLUSIONS
  HLA-A*3101 does not appear to be a predictor for lamotrigine- and phenytoin-induced cADRs in Europeans. Our genome-wide association study results do not support the existence of a clinically relevant common variant for the development of lamotrigine- or phenytoin-induced cADRs. As a predictive marker, HLA-A*3101 appears to be specific for carbamazepine-induced cADRs.
authors.affiliation: The Department of Molecular & Cellular Therapeutics, the Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: McCormack
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Urban
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Nicole
authors.initials: N
authors.lastname: Walley
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Chantal
authors.initials: C
authors.lastname: Depondt
authors.forename: Elijah
authors.initials: E
authors.lastname: Chaila
authors.forename: Gerard D
authors.initials: GD
authors.lastname: O'Conner
authors.forename: Dalia
authors.initials: D
authors.lastname: Kasperavičiūtė
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Radtke
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
authors.forename: Norman
authors.initials: N
authors.lastname: Delanty
authors.forename: Gianpiero L
authors.initials: GL
authors.lastname: Cavalleri
mesh_terms: D054316:Biomarkers, Pharmacological; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000235:genetics*; D055106:Genome-Wide Association Study; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D010672:Phenytoin / Q000009:adverse effects / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D014227:Triazines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D054316:Biomarkers, Pharmacological; D015234:HLA-A Antigens; C506273:HLA-A*31:01 antigen; D014227:Triazines; D002220:Carbamazepine; D010672:Phenytoin; D000077213:Lamotrigine