Association between HLA and Stevens-Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?
Association between HLA and Stevens-Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?
复制标题
南方汉族HLA与卡马西平诱发的Stevens-Johnson综合征的关联：除B*1502外的遗传标记？
DOI：
10.1111/j.1742-7843.2012.00868.x
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Liao, Wei-Ping
中科院分区：
文献类型：
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作者：
Shi, Yi-Wu;Min, Fu-Li;Liao, Wei-Ping
先前的研究表明，卡马西平诱导的StevensJohnson综合征与中毒性表皮坏死松解症（CBZ诱导的SJS/TEN）和中国人的HLA-B*1502之间存在强相关性，而白人和日本人的HLA-A*3101与HLA-B*1502之间无相关性。最近在东南亚报告了CBZ诱导的SJS/TEN HLA-B*1502阴性病例。CBZ诱导的SJS/TEN与B*0702或B*4001之间也有负相关性的报道，提示可能的保护作用。在这里，我们对18例CBZ诱导的SJS/TEN患者进行了HLA-B和HLA-A基因分型，并与CBZ耐受者和中国南方汉族正常对照进行了比较。发现HLA-B*1502与CBZ诱导的SJS/TEN之间有很强的相关性，敏感性为72.2%，特异性为87.1%。然而，我们也发现5例SJS患者（5/18，27.78%）HLA-B*1502阴性。HLA-A*2402存在于16例SJS中的9例（56.25%，包括HLA-B*1502阴性的5例中的3例），这比CBZ耐受对照或一般南方人群的频率显著更高。仅1例SJS携带HLA-A*3101。CBZ诱导的SJS/TEN组和CBZ耐受组之间的平均年龄、性别比和CBZ使用量无统计学差异。在HLA-B*1502阳性但CBZ耐受患者中寻找可能的保护性遗传标记时，我们未能在观察到的HLA等位基因中找到任何重要因素。鉴于HLA-B*1502与CBZ诱导的SJS/TEN之间的相关性，建议在中国汉族人群中开始CBZ治疗前进行基因检测。然而，医生也应该警惕那些HLA-B*1502阴性的SJS/TEN。在HLA-B*1502阴性患者中，CBZ诱导的SJS/TEN的发展的其他因素以及CBZ耐受患者中的保护因素应进一步研究。
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.