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

AIM: 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. MATERIALS & 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*0801 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*020101/-B*350101/-C*040101 haplotype was associated with LTG-induced MPE (pc=0.0048 for LTG-tolerant groups and pc<0.0001 for MM population). CONCLUSION: Our data suggest the HLA-A*020101/-B*350101/-C*040101 haplotype may be a biomarker for LTG-induced MPE and the HLA-C*0801 allele for PHT-induced MPE. We also identified HLA-A*010101 and -A*310102 as candidates alleles associated with CBZ-induced MPE in MM patients. However, further investigations are necessary to confirm these findings.