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Association between HLA and Stevens–Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?
Author(s) -
Shi YiWu,
Min FuLi,
Qin Bin,
Zou Xin,
Liu XiaoRong,
Gao MeiMei,
Wang Qian,
Zhou JueQian,
Liao WeiPing
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2012.00868.x
Subject(s) - carbamazepine , toxic epidermal necrolysis , human leukocyte antigen , allele , medicine , immunology , dermatology , biology , genetics , antigen , epilepsy , gene , psychiatry
Previous studies have demonstrated a strong association between carbamazepine‐induced S tevens– J ohnson 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 C hinese. 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.