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*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). CONCLUSION: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.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Fricke-Galindo I,Martínez-Juárez IE,Monroy-Jaramillo N,Jung-Cook H,Falfán-Valencia R,Ortega-Vázquez A,Alonso-Vilatela ME,López-López M

doi

10.2217/pgs.14.135

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1881-91

issue

15

eissn

1462-2416

issn

1744-8042

journal_volume

15

pub_type

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