Full-Length Original Research
HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese
Article first published online: 20 MAY 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 7, pages 1307–1314, July 2013
How to Cite
Cheung, Y.-K., Cheng, S.-H., Chan, E. J. M., Lo, S. V., Ng, M. H. L. and Kwan, P. (2013), HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia, 54: 1307–1314. doi: 10.1111/epi.12217
- Issue published online: 1 JUL 2013
- Article first published online: 20 MAY 2013
- Manuscript Accepted: 8 APR 2013
- Health and Health Services Research Fund
- Hong Kong Special Administrative Region Government. Grant Number: 07080381
- Antiepileptic drugs;
- Stevens-Johnson syndrome;
- Toxic epidermal necrolysis;
- Human leukocyte antigen
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).
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.
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.
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.