title: GWAS identifies two susceptibility loci for lamotrigine-induced skin rash in patients with epilepsy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These two validated SNPs may be good candidate markers for predicting LTG-induced MPE in epilepsy patients, although further experimental validation is needed.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hui Won
authors.initials: HW
authors.lastname: Jang
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: So Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yang-Je
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung
authors.initials: K
authors.lastname: Heo
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byung In
authors.initials: BI
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kzoo@yuhs.ac.
authors.forename: Won-Joo
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea. Electronic address: jihyni@yuhs.ac.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D003875:Drug Eruptions / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005076:Exanthema / Q000139:chemically induced / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D000077213:Lamotrigine; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D014227:Triazines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine
keywords: Genome wide association study; Lamotrigine; Maculopapular eruption