汉族人群中芳香族抗癫痫药物所致交叉过敏反应与HLA-B*13:01基因型的相关性

Correlation between aromatic antiepileptic-drugs induced cross-reactivity and HLA-B*13:01 genotype in Han population

目的探讨芳香族抗癫痫药物(AEDs)所致交叉过敏反应与人类白细胞抗原(HLA)-A、B、C、DRB1基因型的相关性。方法采用病例对照研究,将广州市第一人民医院、广州医科大学附属第二医院和暨南大学附属第一医院自2016年9月至2020年9月收集的31例因芳香族AEDs(卡马西平、拉莫三嗪、奥卡西平、苯妥英钠、苯巴比妥)所致交叉过敏反应的患者纳入病例组,52例服用上述5种芳香族AEDs后未出现过敏的患者纳入耐受对照组,500例同期未服用AEDs的健康体检者纳入正常对照组。入组人群均为中国汉族人。采用高分辨率测序法分析3组受试者HLA-A、B、C、DRB1基因型,χ^(2)检验或Fisher确切概率法分析上述基因型与交叉过敏反应的相关性。结果病例组患者HLA-B*13:01的阳性率为45.2%(14/31),耐受对照组患者HLA-B*13:01的阳性率为15.4%(8/52),正常对照组患者HLA-B*13:01的阳性率为14.6%(73/500),病例组患者HLA-B*13:01的阳性率显著高于耐受对照组患者和正常对照组患者,差异有统计学意义(Pc<0.017)。除HLA-B*13:01外,未发现其他HLA-A、B、C、DRB1基因型与芳香族抗癫痫药物导致的交叉过敏反应相关。结论HLA-B*13:01是芳香族AEDs导致交叉过敏反应的危险基因型。

Objective To investigate the correlations of human leukocyte antigen(HLA)-A,B,C,and DRB1 genotypes with cross-reactivity caused by aromatic antiepileptic-drugs.Methods A case-control association study was carried out on subjects who accepted treatments/physical examination in our hospitals from September 2016 and September 2020;31 patients with aromatic antiepileptic drugs(carbamazepine,phenytoin,oxcarbazepine,lamotrigine and phenobarbital)-induced cross-reactivity were enrolled as patient group,52 tolerant subjects who took the 5 antiepileptic drugs for more than 3 months without cross-reactivity were chosen as tolerant control group,and 500 healthy volunteers were recruited as normal control group.The ethnicity of all patients and controls was Han Chinese.High-resolution genotyping was performed to compare the HLA-A,B,C,and DRB1 genotypes in subjects of the 3 groups.χ^(2) test or Fisher's exact test were used to analyze the correlations of HLA genes with cross-reactivity caused by aromatic antiepileptic-drugs.Results The presence of HLA-B*13:01 genotype in the patient group,the tolerant control group,and the normal control group was 45.2%(14/31),15.4%(8/52)and 14.6%(73/500),respectively.The presence of HLA-B*13:01 genotype in the patient group was significantly higher as compared with that in the tolerant control group and normal control group(Pc<0.017).No other HLA genotypes were found to be associated with cross-reactivity caused by aromatic antiepileptic-drugs.Conclusion HLA-B*13:01 is the risk genotype for cross-reactivity caused by aromatic antiepileptic-drugs.