The association between AED-induced cutaneous adverse drug reactions and the HLA-A, -B, and -DRB1 alleles among Caucasian patients: a pilot multicenter study

Background A strong association has been reported between HLA-B*1502 and severe cutaneous adverse drug reactions (CADRs) induced by carbamazepine (CBZ) in Han Chinese patients. However, some investigations showed that the HLA-B*1502 allele is not the universal marker for CADRs in European patients. Moreover, HLA-A*3101 was found to be associated with CBZ-induced hypersensitivity reactions among subjects of northern European ancestry. Objective This study aimed to find out the correlation between the human leukocyte antigen (HLA-A, -B, and -DRB1) alleles and antiepileptic drug (AED)-induced CADRs in Caucasian patients. Design and methods Sixteen patients with AED-induced mild CADRs and eight AED-tolerant controls were enrolled. HLA genotyping was performed by the polymerase chain reaction (PCR) sequence-based typing (SBT) method. Results On the basis of frequency, 13 HLA-A alleles, 15 HLA-B, and 15 HLA-DRB1 alleles were detected by genotyping. HLA-B*1502 was not detected in any of the subjects. In the CADRs group, HLA-B*0801 had the highest frequency compared with other alleles, without a statistical difference between CADRs and the AED-tolerant group. Only two patients with CADRs had the HLA-A*3101 allele. Conclusion HLA-B*1502 is probably not the genetic marker for Caucasian patients with AED-induced CADRs. The frequency of HLA-B*0801 was highest in patients with AED-induced mild CADRs. Nevertheless, statistically, no confirmed correlation between HLA-A, -B, and -DRB1 and Caucasian patients with AED-induced CADRs could be made. Because the number of Caucasian subjects was limited in this pilot study, further studies are planned in Germany.