Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China.
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.
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Dan
D
Sun
Department of Science Research and Education, Wuhan Children's Hospital, Wuhan, 430016, China.
Chun-Hua
CH
Yu
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Zhi-Sheng
ZS
Liu
Department of Central Laboratory, Wuhan Children's Hospital, Wuhan, 430016, China.
Xue-Lian
XL
He
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Jia-Sheng
JS
Hu
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Ge-Fei
GF
Wu
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Bing
B
Mao
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Shu-Hua
SH
Wu
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Hui-Hui
HH
Xiang
D000293:Adolescent; D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D059910:HLA-B15 Antigen / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D013262:Stevens-Johnson Syndrome / Q000208:ethnology / Q000209:etiology / Q000235:genetics*
D000927:Anticonvulsants; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine; D000078330:Oxcarbazepine; D010634:Phenobarbital