RGD Reference Report - HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. - Rat Genome Database

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

Authors: Cheung, YK  Cheng, SH  Chan, EJ  Lo, SV  Ng, MH  Kwan, P 
Citation: Cheung YK, etal., Epilepsia. 2013 Jul;54(7):1307-14. doi: 10.1111/epi.12217. Epub 2013 May 20.
RGD ID: 7365090
Pubmed: (View Article at PubMed) PMID:23692434
DOI: Full-text: DOI:10.1111/epi.12217

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 x 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 x 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.



Disease Annotations    

Phenotype Annotations    

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
RT1-CE13  (RT1 class I, locus CE13)

Genes (Mus musculus)
H2-Q4  (histocompatibility 2, Q region locus 4)

Genes (Homo sapiens)
HLA-B  (major histocompatibility complex, class I, B)


Additional Information