HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese

Ying Kit Cheung, Suk Hang Cheng, Ernest J.M. Chan, Su V. Lo, Margaret H.L. Ng, Patrick Kwan

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Abstract

Purpose HLA-B*15:02 screening is recommended before starting carbamazepine in Han Chinese and Southeast Asians because the allele is strongly predictive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by the drug. We examined whether other HLA-B alleles are also involved and whether the association extends to other antiepileptic drugs (AEDs). Methods Cases of SJS/TEN induced by any AEDs were recruited and matched (1:5) with AED-tolerant controls. Carrier rates of HLA-B alleles, determined by direct sequencing, were compared between cases and controls. Results were meta-analyzed with previous studies to examine the associations between HLA-B*15:02 and SJS/TEN induced by phenytoin and lamotrigine. Key Findings A total of 55 cases (27 carbamazepine, 15 phenytoin, 6 lamotrigine, 7 other AEDs) and 275 controls were recruited. In drug-specific analysis, the carrier rate of HLA-B*15:02 was significantly higher in carbamazepine-SJS/TEN cases compared with carbamazepine-tolerant controls (92.3% vs. 11.9%; p = 3.51 × 10 -18; odds ratio (OR) 89.25; 95% confidence interval (CI) 19.25-413.83), and also in phenytoin-SJS/TEN cases compared with phenytoin-tolerant controls (46.7% vs. 20.0%; p = 0.045; OR 3.50; 95% CI 1.10-11.18). Meta-analyses showed a strong association of HLA-B*15:02 with phenytoin-SJS/TEN (p < 3 × 10-4; OR 4.26; 95% CI 1.93-9.39) and, to a lesser extent, lamotrigine-SJS/TEN (p = 0.03; OR 3.59; 95% CI 1.15-11.22). Compared with drug-tolerant controls, the carrier rates of HLA-B*40:01 and HLA-B*58:01 were lower in cases of SJS/TEN induced by carbamazepine (p = 0.004) and other AEDs (p = 0.009), respectively. Significance SJS/TEN induced by carbamazepine and phenytoin is strongly and moderately associated with HLA-B*15:02 in Han Chinese, respectively. Possible protective associations with HLA-B*40:01 and HLA-B*58:01 warrant further investigation.

Original languageEnglish
Pages (from-to)1307-1314
Number of pages8
JournalEpilepsia
Volume54
Issue number7
DOIs
Publication statusPublished - 1 Jul 2013
Externally publishedYes

Keywords

  • Antiepileptic drugs
  • Human leukocyte antigen
  • Pharmacogenetics
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis

Cite this

Cheung, Y. K., Cheng, S. H., Chan, E. J. M., Lo, S. V., Ng, M. H. L., & Kwan, P. (2013). HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia, 54(7), 1307-1314. https://doi.org/10.1111/epi.12217