中国实用儿科杂志

中国实用儿科杂志 ›› 2011, Vol. 26 ›› Issue (02): 108-.

• 论著 • 上一篇    下一篇

芳香族类抗癫痫药诱发Stevens-Johnson综合征与HLA-B*1502基因的相关性研究

  

  1. 武汉市儿童医院，武汉　430016
  • 出版日期:2011-02-06 发布日期:2011-03-03

Association between antiepileptic drug-induced Stevens-Johnson syndrome and HLA-B*1502.　　

  1. Wuhan Children’s Hospital，Wuhan 430016，China
  • Online:2011-02-06 Published:2011-03-03

摘要：

HLA-B*1502基因与芳香族类抗癫痫药（AEDs）诱发的Stevens-Johnson综合征（Stevens-Johnson syndrome，SJS）在华中地区汉族研究对象的相关性研究。方法　2007—2009年武汉市儿童医院神经内科住院就诊的因服用AEDs而导致药物副反应（cADRs）的16例癫痫患儿为cADRs组，其中5例表现为SJS，高敏综合征（HSS）2例和斑丘疹（MPE）9例。同时，按1 ∶ 2的比例收集32例服AEDs无副反应的患儿为AED-耐受组，其年龄、性别及所服用药物与cADRs组匹配；选取38名正常儿童为正常对照组。采用等位基因特异性多重PCR分型技术（ARMS-PCR）检测HLA-B*1502的基因型。结果　5例由芳香族类AEDs所诱导的SJS皆为HLA-B*1502基因阳性，而在AED-耐受组中2例、正常对照组中3例HLA-B*1502基因阳性。HLA-B*1502基因频率在cADRs组（33.3%）明显高于AED-耐受组（6.25%，P <0.05；OR=7.5，95%CI 1.25～44.89）和正常对照组（7.89%，P < 0.05；OR = 5.30，95%CI 1.09～25.84）。若以SJS或表皮性红斑（TEN）为研究对象则检测到HLA-B*1502基因与SJS或TEN有更强的相关性（P < 0.0001；OR = 247.99，95% CI 5.87～3831.70）。若以AED-耐受组为对照组，HLA-B*1502基因预测芳香族类AEDs诱发SJS的敏感性为100%（95%CI 81.5%～100%），特异性为71.4%（95%CI 30%～95%）。HLA-B*1502基因与MPE及HSS无相关性。结论　HLA-B*1502基因与芳香族类AEDs诱导的SJS在华中地区汉族研究对象呈强相关，HLA-B*1502基因可作为由卡马西平为代表的芳香族类AEDs诱发SJS的易感基因，筛查该基因有助于指导癫痫患儿临床个体化药物治疗。

关键词: Stevens-Johnson综合征, HLA-B*1502, 抗癫痫药, 易感基因

Abstract:

We mainly aimed to examine whether HLA-B*1502 gene is associated with Stevens-Johnson Syndrome （SJS） induced by antiepileptic drugs （AEDs） association in Han children in South China mainland. Methods　We enrolled 16 patients with cutaneous adverse drug reactions（cADRs）induced by antiepileptic drugs， including 5 patients with SJS，2 with hypersensitivity syndrome（HSS）and 9 with maculopapular eruption（MPE），from 2007 to 2009. We also included 32 AED-tolerant controls in 2：1 ratio with cases in age，sex，and AEDprescribed. We also included 38 healthy controls. Multiplex amplification refractory mutation system（ARMS-PCR）was used to determine theirgenotypes. Results　We found that 5 patients with SJS were HLA-B*1502 positive while only 2 individuals were positive in AED-tolerant and healthy controls，respectively. The allele frequency of HLA-B*1502 in patients with cADRs was significantly higher compared with AED-tolerant controls（33.3% vs 6.25%，P < 0.05，OR = 7.5，95% CI 1.25～44.89）or with general population（33.3% vs 7.89%，P < 0.05，OR = 5.30，95%CI 1.09 ～25.84）. If we confined patients with AED-induced SJS alone，stronger association between HLA-B*1502 and AED-induced SJS was found in patients （P < 0.0001，OR = 247.99，95%CI 5.87～3831.70）. When the AED-tolerant group was used as the control，HLA-B*1502 allele had 100% sensitivity （95% CI：81.5% ～100%） and 71.4% specificity （95% CI：30% ～95%） for testing AED-induced SJS. HLA-B*1502 was not associated with MPE and HSS. Conclusion　Our findings have further confirmed the strong association of HLA-B*1502 with AED-induced SJS/TEN in Chinese Han children in South China and HLA-B*1502 is a valuable marker for testing AED-induced SJS. This knowledge could be used to guide personalized medicine for children with epilepsy by screening HLA-B*1502 before prescribing AEDs.

Key words: Stevens-Johnson syndrome, HLA-B*1502, antiepileptic drugs, susceptibility gene