摘要
目的比较新疆维吾尔族、汉族、哈萨克族癫痫患儿HLA-B^(*)1502等位基因携带率和等位基因频率差异,评估HLA-B^(*)1502阳性患儿使用芳香环类抗癫痫药物(ASMs)诱发皮肤不良反应的风险。方法回顾性收集2019年1月—2022年8月在我院就诊并在初次使用ASMs前采用荧光染色原位杂交测序技术检测HLA-B^(*)1502TA和HLAB^(*)1502TB基因型及用药指导的患儿460例,分析其基因型与皮肤型药物不良反应发生情况。结果维、汉、哈族癫痫患儿的HLA-B^(*)1502基因突变率分别为47.41%,41.57%和54.84%。哈萨克族癫痫患儿的HLA-B^(*)1502杂合突变型基因显著高于汉族患儿(P<0.05)。维、汉、哈族癫痫患儿的HLA-B^(*)1502野生型基因组的体重指数均显著高于突变组患儿(P<0.05)。247例HLA-B^(*)1502野生型患儿继续服用芳香族ASMs后未发生皮肤不良反应,12例HLA-B^(*)1502纯合突变型患儿调整为其他作用机制的ASMs,201例HLA-B^(*)1502杂合突变型患儿中仍有56例继续使用芳香族ASMs,有5例患儿在用药3周内发生了斑丘疹、Stevens-Johnson综合征、中毒性表皮坏死松解症。结论临床初次使用芳香族ASMs控制和治疗患儿癫痫发作过程中,有必要进行HLA-B^(*)1502基因检测。
Objective To compare the HLA-B^(*)1502 allele carrier rate and allele frequency in Uygur,Han and Kazak children with epilepsy,and to evaluate the risk of inducing adverse skin reactions by using aromatic ring anti-seizure medications(ASMs)in HLA-B^(*)1502-positive children.Methods 460 children who were treated in our hospital from January 2019to August 2022,were detected HLA-B^(*)1502TA and HLA-B^(*)1502TB genotypes by fluorescent staining in situ hybridization sequencing technology before the first use of ASMs and were implemented medication guidance were retrospectively collected,and their genotypes and skintype adverse drug reactions were analyzed.Results The mutation rates of HLA-B^(*)1502 gene in children with Uyghur,Han and Kazakh epilepsy were 47.41%,41.57%and 54.84%,respectively.The HLA-B^(*)1502 heterozygous mutant gene in Kazakh children with epilepsy was significantly higher than that in Han children(P<0.05).The body mass indices of HLA-B^(*)1502 wild-type genomes of children with Uyghur,Han and Kazakh epilepsy were significantly higher than those of children in the mutant group(P<0.05).247 wild-type children with HLA-B^(*)1502 did not develop skin adverse reactions after continuing to take aromatic ASMs,12 children with HLA-B^(*)1502 homozygous mutant adjusted to ASMs with other mechanisms of action,56 of the201 heterozygous mutant patients continued to use aromatic ASMs,and 5 children developed maculopapular rash,Stevens Johnson syndrome and toxic epidermal necrolysis within three weeks of medication.Conclusion HLA-B^(*)1502 gene testing is necessary for the initial clinical use of aromatic ASMs for the control and treatment of seizures in children.
作者
赵婷
李红健
孙岩
王婷婷
冯杰
张惠兰
白慧东
朱卫江
李燕菊
于鲁海
Ting ZHAO;Hong-Jian LI;Yan SUN;Ting-Ting WANG;Jie FENG;Hui-Lan ZHANG;Hui-Dong BAI;Wei-Jiang ZHU;Yan-Ju LI;Lu-Hai YU(Department of Pharmacy,People’s Hospital of Xinjiang Uygur Autonomous Region(Institute of Clinical Pharmacy of Xinjiang Uygur Autonomous Region),Urumqi 830001,China;Department of Neurology,Children's Hospital of Xinjiang Uygur Autonomous Region(Xinjiang Hospital of Beijing Children’Hospital),Urumqi 830001,China)
出处
《药物流行病学杂志》
CAS
2023年第2期151-157,共7页
Chinese Journal of Pharmacoepidemiology
基金
国家自然科学基金地区科学基金项目(81460571)。
