实用医学杂志 ›› 2021, Vol. 37 ›› Issue (16): 2080-2088.doi: 10.3969/j.issn.1006⁃5725.2021.16.009

• 临床研究 • 上一篇    下一篇

奥卡西平导致的皮肤不良反应与HLA⁃B*1502、HLA⁃B*1301基因的关系

民福利1, 王晓2, 范翠霞3, 郭静4, 秦兵2   

  1. 1 广州市第一人民医院神经内科(广州 510000);2 暨南大学附属第一医院神经外科癫痫中心 (广州 510000);3 广州医科大学附属第二医院神经科学研究所(广州 510260);4 广东三九脑科医院 癫痫中心(广州 510510)


  • 出版日期:2021-08-25 发布日期:2021-08-25
  • 通讯作者: 秦兵 E⁃mail:qb900@163.com
  • 基金资助:
    国家自然青年科学基金项目(编号:81601136);广州市卫生健康科技项目(编号:20211A011009)

Association of HLA⁃B*1502 and HLA⁃B*1301 genes with oxcarbazepine⁃induced cutaneous adverse reac⁃ tions MIN Fuli

WANG Xiao,FAN Cuixia,GUO Jing,QIN Bing.   

  1. Department of Neurology,Guangzhou First People′s Hospital,Guangzhou 510000,China

  • Online:2021-08-25 Published:2021-08-25
  • Contact: QIN Bing E⁃mail:qb900@163.com

摘要:

目的 探讨奥卡西平(oxcarbazepine,OXC)导致的皮肤不良反应(cutaneous adverse reactions cADRs)与 HLA⁃B*1502、HLA⁃B*1301 基因的关系。方法 采用病例对照研究,联合多中心于 2017 1 2020 12 月募集服用 OXC 后出现 cADRs 的患者、OXC 耐受患者和健康体检者。提取外周血 DNA,采用聚合酶链反应(PCR)和 Sanger 测序法检测 HLA⁃B 基因型;采用χ2 检验比较病例组和耐受对照组、病例组和健康对照组之间HLA⁃B*1502、HLA⁃B*1301阳性率的差异。结果 募集到15 OXC⁃cADRs、64例OXC 耐受者及 100 例健康体检者。1 OXC 导致 Stevens⁃Johnson 综合症(SJS)/中毒性表皮坏死松解症(TEN)患者为 HLA⁃B*1502 基因阳性,14 OXC 导致轻度斑丘疹(maculopapular exanthem,MPE)患者中 HLA⁃B*1502 基因阳性率为 14.29%(2/14),HLA⁃B*1502 的阳性率在 OXC 导致 MPE 组与 OXC 耐受对照组、正常对照组之 间的差异无统计学意义(P>0.05)。OXC⁃MPE 组的 HLA⁃B*1301 基因阳性率为 42.86%,显著高于 OXC 受组及正常对照组(均 P<0.05)。结论 OXC 导致 SJS/TEN 可能与 HLA⁃B*1502 有关系;OXC 导致 MPE 能与HLA⁃B*1301有关系

关键词:

奥卡西平, 轻度皮疹, SJS/TEN, HLA?B*1502, HLA?B*1301

Abstract:

Objective To explore the association of oxcarbazepine(OXC)⁃ induced cutaneous adverse reactions(CARs)with HLA ⁃B*1502 and HLA ⁃B*1301 genes. Methods A multicenter case ⁃control study was performed. Patients with OXC ⁃induced CARs,OXC ⁃tolerant patients,and healthy controls were recruited from January 2017 to December 2020. DNAs were extracted from peripheral blood. The genotype of HLA⁃B was detected by polymerase chain reaction(PCR)and Sanger sequencing. Chi⁃square test and Fisher′s exact test were used to compare the differences in the rate of HLA⁃B*1502 and HLA⁃B*1301 alleles between OXC⁃induced CARs group and OXC⁃tolerant group or normal control group. Results 15 patients with OXC⁃induced CARs,64 OXC⁃tolerant patients,and 100 healthy individuals were included in this study. One patient with OXC⁃induced SJS/TEN carried HLA⁃B*1502 gene. The rate of HLA⁃B *1502 gene in mild OXC⁃induced MPE group was 14.28%(2/14),which was not significantly higher than that in OXC ⁃tolerant group or normal control group(P > 0.05 for both compari⁃ sons). The rate of HLA ⁃B*1301 gene was 42.86% in OXC ⁃induced CARs group,which was significantly higher than that in OXC⁃tolerant group or normal control group(P < 0.05). Conclusions HLA⁃B*1502 was probably associated with OXC induced SJS/TEN,whereas HLA⁃B*1301 was related to OXC⁃induced MPE.

Key words:

oxcarbazepine, MPE, SJS/TEN, HLA?B*1502, HLA?B*1301