title: HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican Mestizo patients.
abstract: OBJECTIVE
  Several HLA alleles have been associated with antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) in different populations; however, this has not been investigated in Mexican Mestizos (MM). Thus, the purpose of this preliminary study was to determine the association of HLA class I alleles with AED-induced cADRs in MM patients.
  
  
  METHODS
  This case-control association study included 21 MM patients with phenytoin (PHT)-, carbamazepine (CBZ)-, or lamotrigine (LTG)-induced maculopapular exanthema (MPE) or Stevens-Johnson syndrome (SJS); 31 MM patients tolerant to the same AEDs; and 225 unrelated, healthy MM volunteers. HLA class I genotyping was performed. Differences in HLA allele frequencies between AED-induced cADR patients and AED-tolerant patients were assessed. Frequencies of alleles possibly associated with AED-induced cADRs in MM patients were compared with those in MM population.
  
  
  RESULTS
  The frequency of HLA-C*08:01 allele in PHT-induced MPE was higher than that in the PHT-tolerant group (pc=0.0179) or in the MM population (pc<0.0001). For the first time, HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype was associated with LTG-induced MPE (pc=0.0048 for LTG-tolerant groups and pc<0.0001 for MM population).
  
  
  CONCLUSIONS
  Our data suggest the HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype may be a biomarker for LTG-induced MPE and the HLA-C*08:01 allele for PHT-induced MPE. We also identified HLA-A*01:01:01 and -A*31:01:02 as candidates alleles associated with CBZ-induced MPE in MM patients. However, further investigations are necessary to confirm these findings.
authors.affiliation: Maestría en Ciencias Farmacéuticas, Universidad Autónoma Metropolitana, Unidad Xochimilco, Calzada del Hueso 1100, Coyoacán, México, D.F., 04960, México.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fricke-Galindo
authors.forename: Iris E
authors.initials: IE
authors.lastname: Martínez-Juárez
authors.forename: Nancy
authors.initials: N
authors.lastname: Monroy-Jaramillo
authors.forename: Helgi
authors.initials: H
authors.lastname: Jung-Cook
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortega-Vázquez
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Alonso-Vilatela
authors.forename: Marisol
authors.initials: M
authors.lastname: López-López
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects; D003875:Drug Eruptions / Q000235:genetics* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine
keywords: Mexican Mestizo; Stevens–Johnson syndrome; antiepileptic drug; carbamazepine; cutaneous adverse drug reaction; exanthema maculopapular; human leukocyte antigen; lamotrigine; pharmacogenetics; phenytoin