海南地区癫痫儿童HLA-B*1502基因与芳香族抗癫痫药物治疗后皮肤型药物不良反应的相关性研究

Correlation between HLA-B*1502 gene and cutaneous adverse drug reactions after treatment of aromatic antiepileptic drugs in children with epilepsy in Hainan area

目的探讨海南地区癫痫儿童HLA-B*1502基因与芳香族抗癫痫药物(AEDs)治疗后发生皮肤型药物不良反应(cADRs)的相关性。方法纳入本院2020年1月—2022年7月收治的癫痫儿童100例,均使用芳香族AEDs治疗,并根据是否发生cADRs分为cADRs组(n=32)与非cADRs组(n=68)。针对患儿进行HLA-B*1502基因检测,记录HLA-B*1502基因分型与等位基因频率。根据cADRs的严重程度,将轻微反应者纳入轻微组,将Stevens-Johnson综合征(SJS)、中毒性表皮坏死松解症(TEN)以及药物超敏综合征(DHS)者纳入重型组。比较不同严重程度患儿的HLA-B*1502基因分型;分析HLA-B*1502基因与cADRs的相关性。结果cADRs组HLA-B*1502TB位点的CT型比率高于非cADRs组(68.75%、36.76%),CC型比率低于非cADRs组(28.13%、63.24%),差异有统计学意义(P<0.05)。cADRs组HLA-B*1502TB位点的T等位基因频率为37.50%,高于非cADRs组的18.38%,差异有统计学意义(P<0.05)。轻微组与重型组HLA-B*1502基因的基因分型及等位基因频率比较,差异无统计学意义(P>0.05)。Logistic回归分析显示,HLA-B*1502TB位点的CT基因分型及T等位基因会增加海南地区癫痫儿童AEDs治疗后cADRs的发生风险(P<0.05)。结论海南地区癫痫儿童经芳香族AEDs治疗后,cADRs的发生与HLA-B*1502基因密切相关。HLA-B*1502TB位点携带CT基因分型与T等位基因的患儿的cADRs发生风险更高。

Objective To investigate the correlation between HLA-B*1502 gene and cutaneous adverse drug reactions(cADRs)after treatment of aromatic antiepileptic drugs(AEDs)in children with epilepsy in Hainan area.Methods A total of 100 children with epilepsy in our hospital from January 2020 to July 2022 were enrolled and treated with aromatic AEDs,and they were divided into cADRs group(n=32)and non-CADRs group(n=68)according to the occurrence of cADRs.HLA-B*1502 gene test was performed for the children,and HLA-B*1502 genotype and allele frequency were recorded.According to the severity of cADRs,the children with mild reactions were included in mild group,and the children with Stevens-Johnson syndrome(SJS),toxic epidermal necrolysis(TEN)and drug hypersensitivity syndrome(DHS)were included in severe group.HLA-B*1502 genotypes in the children with different severity levels were compared;the correlation between HLA-B*1502 gene and cADRs was analyzed.Results The proportion of CT type in HLA-B*1502TB locus in the cADRs group was significantly higher than that in the non-cADRs group(68.75%versus 36.76%),while theproportion of CC type was significantly lower than that in the non-cADRs group(28.13%versus 63.24%)(P<0.05).T allele frequency of HLA-B*1502TB locus in the cADRs group was 37.50%,which was significantly higher than 18.38%in the non-cADRs group(P<0.05).There were no significant differences in genotype and allele frequency of HLA-B*1502 gene between the mild group and the severe group(P>0.05).Logistic regression analysis showed that CT genotype and T allele of HLA-B*1502TB locus can increase the occurrence risk of cADRs after AEDs treatment in children with epilepsy in Hainan area(P<0.05).Conclusion After treatment of aromatic AEDs,the occurrence of cADRs in children with epilepsy in Hainan area is closely related to the HLA-B*1502 gene.Children with CT genotype and T allele at HLA-B*1502TB locus have a higher occurrence risk of cADRs.