Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions

Pharmacogenomics. 2012 Mar;13(4):399-405. doi: 10.2217/pgs.11.165.


Aims: 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.

Materials & 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Pharmacological
  • Carbamazepine / adverse effects
  • Carbamazepine / therapeutic use
  • Drug Hypersensitivity / genetics*
  • Genome-Wide Association Study*
  • HLA-A Antigens / genetics*
  • Humans
  • Lamotrigine
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use
  • Polymorphism, Single Nucleotide
  • Triazines / adverse effects*
  • Triazines / therapeutic use


  • Biomarkers, Pharmacological
  • HLA-A Antigens
  • HLA-A*31:01 antigen
  • Triazines
  • Carbamazepine
  • Phenytoin
  • Lamotrigine