Association of HLA-B*1502 and *1511 Allele with Antiepileptic Drug-induced Stevens-Johnson Syndrome in Central China

摘要

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 phenobabital(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.