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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

    摘要
  • 摘要:
    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。

     

    Abstract:
    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  he 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.

     

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