GWAS identifies two susceptibility loci for lamotrigine-induced skin rash in patients with epilepsy

Epilepsy Res. 2015 Sep:115:88-94. doi: 10.1016/j.eplepsyres.2015.05.014. Epub 2015 Jun 2.

Abstract

Purpose: Lamotrigine (LTG)-induced maculopapular eruption (MPE) often causes treatment discontinuation and rising burdens on current healthcare systems. We conducted a genome-wide association study to identify novel susceptibility loci associated with LTG-induced MPE in patients with epilepsy.

Materials and methods: We enrolled patients with LTG-induced MPE (n=34) and utilized the Korea Association Resource project cohort as a control group (n=1214). We explored associations between LTG-induced MPE and single nucleotide polymorphisms (SNPs) through imputation and replicated these associations in samples from 59 LTG-induced MPE cases and 98 LTG tolerant-controls.

Results: We found two novel SNPs associated with LTG-induced MPE: rs12668095 near CRAMP1L/TMEM204/IFT140/HN1L (P=4.89×10(-7)) and rs79007183 near TNS3 (P=3.15×10(-10)), both of which were replicated in an independent cohort.

Conclusion: These two validated SNPs may be good candidate markers for predicting LTG-induced MPE in epilepsy patients, although further experimental validation is needed.

Keywords: Genome wide association study; Lamotrigine; Maculopapular eruption.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Asian People / genetics
  • Cohort Studies
  • Drug Eruptions / genetics*
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Exanthema / chemically induced
  • Exanthema / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lamotrigine
  • Polymorphism, Single Nucleotide*
  • Republic of Korea
  • Triazines / adverse effects*
  • Triazines / therapeutic use

Substances

  • Anticonvulsants
  • Triazines
  • Lamotrigine