Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, Guangzhou, China.
Basic Clin Pharmacol Toxicol. 2012 Jul;111(1):58-64. doi: 10.1111/j.1742-7843.2012.00868.x. Epub 2012 Mar 17.
Previous studies have demonstrated a strong association between carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-induced SJS/TEN) and HLA-B1502 in Chinese, and HLA-A3101 but not HLA-B1502 in Caucasians and Japanese. Cases with CBZ-induced SJS/TEN negative for HLA-B1502 were reported recently in Southeast Asia. Negative correlations between CBZ-induced SJS/TEN and B0702 or B4001 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-B1502 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-B1502. HLA-A2402 was present in nine of 16 cases with SJS (56.25%, including three of five cases negative for HLA-B1502), which was significantly more frequent than that of CBZ-tolerant controls or the general southern population. Only one case with SJS carried HLA-A3101. 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-B1502-positive but CBZ-tolerant patients, we failed to find any significant factors in the HLA alleles observed. Given the association between HLA-B1502 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-B1502. 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.
先前的研究表明，卡马西平诱导的史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症（CBZ 诱导的 SJS/TEN）与中国人中的 HLA-B1502 以及高加索人和日本人中的 HLA-A3101 之间存在很强的关联，但与 HLA-B1502 无关。最近在东南亚报道了 HLA-B1502 阴性的 CBZ 诱导 SJS/TEN 病例。还报道了 CBZ 诱导的 SJS/TEN 与 B0702 或 B4001 之间的负相关关系，提示其可能具有保护作用。在此，我们对 18 例 HLA-B 和 HLA-A 基因型的 CBZ 诱导 SJS/TEN 患者进行了基因分型，并与南方汉族的 CBZ 耐受和正常对照组进行了比较。发现 HLA-B1502 与 CBZ 诱导的 SJS/TEN 之间存在很强的关联，敏感性为 72.2%，特异性为 87.1%。然而，我们还发现了 5 例 SJS 患者（5/18，27.78%）HLA-B1502 阴性。HLA-A2402 存在于 16 例 SJS 患者中的 9 例（56.25%，包括 3 例 HLA-B1502 阴性）中，明显高于 CBZ 耐受对照组或一般南方人群。只有 1 例 SJS 患者携带 HLA-A3101。CBZ 诱导的 SJS/TEN 组和 CBZ 耐受组在平均年龄、性别比例和 CBZ 使用率方面无统计学差异。在寻找 HLA-B1502 阳性但 CBZ 耐受患者中可能存在的保护性遗传标记时，我们未能发现观察到的 HLA 等位基因中有任何显著因素。鉴于 HLA-B1502 与 CBZ 诱导的 SJS/TEN 之间的关联，建议在汉族人群中在开始 CBZ 治疗前进行基因检测。然而，医生也应该对 HLA-B1502 阴性的患者警惕 SJS/TEN 的发生。还应进一步研究 HLA-B*1502 阴性患者中 CBZ 诱导的 SJS/TEN 的发展和 CBZ 耐受患者的保护因素。
