Anticonvulsants/adverse effects* ; Anticonvulsants/therapeutic use ; Asian Continental Ancestry Group/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 ; Polymorphism, Single Nucleotide* ; Republic of Korea ; Triazines/adverse effects* ; Triazines/therapeutic use
Keywords
Genome wide association study ; Lamotrigine ; Maculopapular eruption
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.