Association between HLA and Stevens-Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?

作者:Shi, Yi-Wu; Min, Fu-Li; Qin, Bin; Zou, Xin; Liu, Xiao-Rong; Gao, Mei-Mei; Wang, Qian; Zhou, Jue-Qian; Liao, Wei-Ping*
来源:Basic and Clinical Pharmacology and Toxicology, 2012, 111(1): 58-64.
DOI:10.1111/j.1742-7843.2012.00868.x

摘要

Previous studies have demonstrated a strong association between carbamazepine-induced StevensJohnson syndrome and toxic epidermal necrolysis (CBZ-induced SJS/TEN) and HLA-B*1502 in Chinese, and HLA-A*3101 but not HLA-B*1502 in Caucasians and Japanese. Cases with CBZ-induced SJS/TEN negative for HLA-B*1502 were reported recently in Southeast Asia. Negative correlations between CBZ-induced SJS/TEN and B*0702 or B*4001 have also been reported, suggesting a possible protective role. Here, we genotyped HLA-B and HLA-A in 18 cases with CBZ-induced SJS/TEN, in comparison with CBZ-tolerant and normal controls in Southern Han Chinese. A strong association between HLA-B*1502 and CBZ-induced SJS/TEN was found, with 72.2% sensitivity and 87.1% specificity. However, we also found five patients with SJS (5/18, 27.78%) who were negative for HLA-B*1502. HLA-A*2402 was present in nine of 16 cases with SJS (56.25%, including three of five cases negative for HLA-B*1502), which was significantly more frequent than that of CBZ-tolerant controls or the general southern population. Only one case with SJS carried HLA-A*3101. No statistical difference in the mean age, sex ratio and CBZ usage was found between the CBZ-induced SJS/TEN group and the CBZ-tolerant group. In search for possible protective genetic markers in HLA-B*1502-positive but CBZ-tolerant patients, we failed to find any significant factors in the HLA alleles observed. Given the association between HLA-B*1502 and CBZ-induced SJS/TEN, genetic testing before initiating CBZ therapy is suggested in Han Chinese population. However, physicians should also be vigilant about SJS/TEN in those negative for HLA-B*1502. Other factors for the development of CBZ-induced SJS/TEN in HLA-B*1502-negative patients and protective factors in CBZ-tolerant patients should be investigated further.