HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.
HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.
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HLA-A24:02是抗癫痫药物引起的皮肤不良反应的常见危险因素
DOI：
10.1212/wnl.0000000000004008
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发表时间：
2017-06-06
期刊：
影响因子：
9.9
通讯作者：
Liao WP
中科院分区：
文献类型：
--
作者：
Shi YW;Min FL;Zhou D;Qin B;Wang J;Hu FY;Cheung YK;Zhou JH;Hu XS;Zhou JQ;Zhou LM;Zheng ZZ;Pan J;He N;Liu ZS;Hou YQ;Lim KS;Ou YM;Hui-Ping Khor A;Ng CC;Mao BJ;Liu XR;Li BM;Kuan YY;Yi YH;He XL;Deng XY;Su T;Kwan P;Liao WP
研究人类白细胞抗原（HLA）基因座在芳香族抗癫痫药物引起的皮肤不良反应中的作用。进行了一项病例对照研究，以检测中国南方汉族人群中与芳香族抗癫痫药物诱发的 Stevens-Johnson 综合征相关的 HLA 基因座。 2006年1月1日至2015年12月31日期间，来自8个中心的91例芳香族抗癫痫药物诱发的Stevens-Johnson综合征患者和322例匹配的耐药对照被纳入研究。在斑丘疹病例和其他人群数据的荟萃分析中重复了重要的基因型。基于序列的分型确定了 HLA-A、HLA-B、HLA-C 和 HLA-DRB1 基因型。 HLA-B*15:02 被证实与卡马西平诱发的 Stevens-Johnson 综合征密切相关 (p = 5.63 × 10−15)。此外，HLA-A*24:02 与芳香族抗癫痫药物组（p = 1.02 × 10−5）和单独药物（卡马西平 p = 0.015、拉莫三嗪 p = 0.005、苯妥英 p = 0.027）诱发的 Stevens-Johnson 综合征显着相关。 Logistic 回归分析显示 HLA-B*15:02 和 HLA-A*24:02 之间存在乘法相互作用。 HLA-A*24:02 和/或 HLA-B*15:02 的阳性显示敏感性为 72.5%，特异性为 69.0%。斑丘疹病例中 HLA-A*24:02 的存在也显着高于对照组 (p = 0.023)。对日本、韩国、马来西亚、墨西哥、挪威和中国数据的荟萃分析显示了类似的关联。 HLA-A*24:02是南方汉族和其他民族人群中芳香族抗癫痫药物引起皮肤不良反应的常见遗传危险因素。建议中国南方人群进行治疗前筛查。
To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug–induced cutaneous adverse reactions. A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug–induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes. HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10−15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10−5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association. HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.