Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China

J Huazhong Univ Sci Technolog Med Sci. 2014 Feb;34(1):146-150. doi: 10.1007/s11596-014-1247-7. Epub 2014 Feb 6.


Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B*1502 in Han Chinese. Here, we extended the study of HLA-B*1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobarbital (PB). In addition, we genotyped HLA-B*1511 in a case of CBZ-induced SJS with genotype negative for HLA-B*1502. The presence of HLA-B*1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B*1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant (n=32) and normal controls (n=38) in the central region of China. The data showed that HLA-B*1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B*1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06-36.74) and 4.86 (95% CI: 1.01-23.47). The sensitivity and specificity of HLA-B*1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B*1502 was not found in 11 children with maculopapular exanthema (MPE) (n=9) and hypersensitivity syndrome (HSS) (n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B*1502 but carried HLA-B*1511. It was suggested that the association between the CBZ-induced SJS and HLA-B*1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B*1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B*1502.

MeSH terms

  • Adolescent
  • Alleles
  • Anticonvulsants / adverse effects*
  • Asian People / genetics
  • Carbamazepine / adverse effects
  • Carbamazepine / analogs & derivatives
  • Child
  • Child, Preschool
  • China
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HLA-B15 Antigen / genetics*
  • Humans
  • Infant
  • Male
  • Oxcarbazepine
  • Phenobarbital / adverse effects
  • Polymerase Chain Reaction
  • Stevens-Johnson Syndrome / ethnology
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*


  • Anticonvulsants
  • HLA-B*15:02 antigen
  • HLA-B15 Antigen
  • Carbamazepine
  • Oxcarbazepine
  • Phenobarbital