抗癫痫药物皮肤不良反应与HLA-B~*1502基因的相关性研究
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摘要
目的通过临床研究分析探讨芳香族抗癫痫药物所诱发的皮肤不良反应与患者HLA-B*1502基因之间的相关性。方法选取从2015年4月～2017年10月于我院就诊治疗的发生癫痫的患者581例为研究对象,使用了AEDs类抗癫痫药物进行了治疗,发生皮肤不良反应的有95例,未发生皮肤不良反应的患者有486例,在发生皮肤不良反应的患者中MPE有49例,SJS有27例,TEN有19例,对以上患者进行基本资料及HLA-B*1502基因的分析,采用统计软件进行统计分析,确定皮肤不良发应与HLA-B*1502基因之间的相关性。结果研究结果表明,SJS以及TEN皮肤不良反应的发生与HLA-B*1502之间具有明显的相关性,而MPE不良反应的发生与该基因无明确的相关性。结论在临床上使用AEDs类抗癫痫药进行抗癫痫治疗时,可以提前检测患者HLA-B*1502基因,从而达到预测其皮肤不良反应的作用,根据利弊平衡使用该类药物进行抗癫痫治疗。
Objective To discuss the correlation between skin adverse reactions and HLA-B*1502 gene of antiepileptic drugs by clinical research. Methods 581 patients with epilepsy admitted for treatment from April 2015 to October 2017 were selected as subjects.After being treated with AEDs antiepileptic drugs,there were 95 cases of skin adverse reactions while 486 cases were free from the reaction.Among the 95 cases of skin adverse reactions,there were 49 cases of MPE,27 cases of SJS and 19 cases of TEN.The basic data and HLA-B*1502 gene of the above patients were analyzed by statistical software,and the correlation between the skin adverse reactions and HLA-B*1502 gene was determined. Results The results of the study showed a significant correlation between skin adverse reactions of SJS,TEN and HLA-B*1502 gene,while proved no clear correlation between the MPE and HLA-B*1502. Conclusion The application of AEDs antiepileptic drugs for clinical treatment and the detection of HLA-B*1502 gene in advance can predict the skin adverse reactions in antiepileptic treatment.
Objective To discuss the correlation between skin adverse reactions and HLA-B*1502 gene of antiepileptic drugs by clinical research. Methods 581 patients with epilepsy admitted for treatment from April 2015 to October 2017 were selected as subjects.After being treated with AEDs antiepileptic drugs,there were 95 cases of skin adverse reactions while 486 cases were free from the reaction.Among the 95 cases of skin adverse reactions,there were 49 cases of MPE,27 cases of SJS and 19 cases of TEN.The basic data and HLA-B*1502 gene of the above patients were analyzed by statistical software,and the correlation between the skin adverse reactions and HLA-B*1502 gene was determined. Results The results of the study showed a significant correlation between skin adverse reactions of SJS,TEN and HLA-B*1502 gene,while proved no clear correlation between the MPE and HLA-B*1502. Conclusion The application of AEDs antiepileptic drugs for clinical treatment and the detection of HLA-B*1502 gene in advance can predict the skin adverse reactions in antiepileptic treatment.
引文
[1]曹凤,吴方建.某院住院患者抗癫痫药物临床应用药物相关问题的调查分析[J].中国药师,2018,21(2):268-272.
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[6]Teh LK,Selvaraj M,Bannur Z,et al.Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02.Journal of pharmacy&pharmaceutical sciences:a publication of the Canadian Society for Pharmaceutical Sciences[J].Societe canadienne des sciences pharmaceutiques,2016,19(1):147-160.
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[8]甘水根.抗癫痫药物皮肤不良反应与HLA-B~*1502基因的相关性研究[D].南昌:南昌大学,2014:20-22.
[9]Nguyen DV,Vidal C,Chi HC,et al.A novel multiplex polymerase chain reaction assay for detection of both HLA-A*31:01/HLA-B*15:02 alleles,which confer susceptibility to carbamazepine-induced severe cutaneous adverse reactions[J].Hla,2017,90(6):335-42.
[10]Khor AH,Lim KS,Tan CT,et al.HLA-A*31:01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population[J].Pharmacogenetics and genomics,2017,27(7):275-278.
[11]Ramirez E,Bellon T,Tong HY,et al.Significant HLAclass I type associations with aromatic antiepileptic drug(AED)-induced SJS/TEN are different from those found for the same AED-induced DRESS in the Spanish population[J].Pharmacological research,2017,115(27):168-178.
[12]Yip VL,Pirmohamed M.The HLA-A*31:01 allele:influence on carbamazepine treatment[J].Pharmacogenomics and personalized medicine,2017,10(9):29-38.
[13]吴欣桐,胡发云,周东,等.HLA-A-B-DRB1单倍型与抗癫痫药物所致皮肤不良反应间的关系[J].西部医学,2015,27(6):816-821.
[14]毕津莲,陈艳,张秀芹,等.芳香族抗癫痫药物致皮肤不良反应的研究进展[J].中国现代医学杂志,2015,25(33):60-64.
[15]甘水根,蔡兰云.抗癫药物皮肤不良反应与HLA基因的关系进展[J].南昌大学学报(医学版),2013,53(5):91-93.
[2]吴冬燕,朱国行.抗癫痫药物的分类、作用机制与不良反应[J].上海医药,2015,36(9):3-7.
[3]侯蕴祈,石海琴,杨红姬等.HLA-B*1502表达与AEDs致敏相关性的临床研究[J].中风与神经疾病杂志,2017,34(12):1090-1092.
[4]Wang Q,Sun S,Xie M,et al.Association between the HLA-B alleles and carbamazepine-induced SJS/TEN:Ameta-analysis[J].Epilepsy research,2017,135(9):19-28.
[5]Gui H,Kwok M,Baum L,et al.SNP-based HLA allele tagging,imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese[J].The pharmacogenomics journal,2018,18(2):340-346.
[6]Teh LK,Selvaraj M,Bannur Z,et al.Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02.Journal of pharmacy&pharmaceutical sciences:a publication of the Canadian Society for Pharmaceutical Sciences[J].Societe canadienne des sciences pharmaceutiques,2016,19(1):147-160.
[7]黄亚莉,任惠.芳香族抗癫痫药物所致严重皮肤不良反应的研究进展[J].癫痫杂志,2017,3(4):325-328.
[8]甘水根.抗癫痫药物皮肤不良反应与HLA-B~*1502基因的相关性研究[D].南昌:南昌大学,2014:20-22.
[9]Nguyen DV,Vidal C,Chi HC,et al.A novel multiplex polymerase chain reaction assay for detection of both HLA-A*31:01/HLA-B*15:02 alleles,which confer susceptibility to carbamazepine-induced severe cutaneous adverse reactions[J].Hla,2017,90(6):335-42.
[10]Khor AH,Lim KS,Tan CT,et al.HLA-A*31:01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population[J].Pharmacogenetics and genomics,2017,27(7):275-278.
[11]Ramirez E,Bellon T,Tong HY,et al.Significant HLAclass I type associations with aromatic antiepileptic drug(AED)-induced SJS/TEN are different from those found for the same AED-induced DRESS in the Spanish population[J].Pharmacological research,2017,115(27):168-178.
[12]Yip VL,Pirmohamed M.The HLA-A*31:01 allele:influence on carbamazepine treatment[J].Pharmacogenomics and personalized medicine,2017,10(9):29-38.
[13]吴欣桐,胡发云,周东,等.HLA-A-B-DRB1单倍型与抗癫痫药物所致皮肤不良反应间的关系[J].西部医学,2015,27(6):816-821.
[14]毕津莲,陈艳,张秀芹,等.芳香族抗癫痫药物致皮肤不良反应的研究进展[J].中国现代医学杂志,2015,25(33):60-64.
[15]甘水根,蔡兰云.抗癫药物皮肤不良反应与HLA基因的关系进展[J].南昌大学学报(医学版),2013,53(5):91-93.