• Epilepsy & behavior : E&B · Aug 2014

    Genetic predictors of Stevens-Johnson syndrome and toxic epidermal necrolysis induced by aromatic antiepileptic drugs among the Chinese Han population.

    • Wei Wang, Fa-Yun Hu, Xin-Tong Wu, Dong-Mei An, Bo Yan, and Dong Zhou.
    • Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
    • Epilepsy Behav. 2014 Aug 1; 37: 16-9.

    BackgroundPrevious studies suggested that one or more HLA alleles participate in the pathogenesis of AED-induced SJS/TEN, but most of these studies focused only on the HLA-B alleles.PurposeThe aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across a broader spectrum of HLA alleles, including the HLA-A, -B and -DRB1 alleles, to further explore the association between each HLA allele and SJS/TEN induced by aromatic AEDs.MethodsA total of 27 patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN, two PHT-SJS/TEN, and two PB-SJS/TEN patients) and 64 patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject.ResultsFifteen subjects in the SJS/TEN group (12 exhibiting CBZ-SJS/TEN, two exhibiting LTG-SJS, and one exhibiting PB-SJS) carried the HLA-B*15:02 allele, whereas only 4/64 subjects in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Nine patients in the SJS/TEN group carried the HLA-DRB1*15:01 allele, while 12/64 subjects in the tolerant group carried this allele; considering that two patients in the SJS/TEN group (one exhibiting LTG-SJS and one exhibiting PB-SJS) were homozygous for this allele, the prevalence of HLA-DRB1*15:01 expression between the two groups was significantly different (P=0.041). Furthermore, the carrier rates of HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 were lower in the SJS/TEN group compared with the AED-tolerant group. The carrier rates of these alleles between the two groups were significantly different (P=0.009, 0.016, and 0.009, respectively).ConclusionsThe HLA-DRB1*15:01 allele may represent a risk factor for AED-induced SJS/TEN among Han Chinese. The HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 alleles may be "protectors" against AED-induced SJS/TEN, especially CBZ-SJS/TEN.Copyright © 2014 Elsevier Inc. All rights reserved.

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