中国南方汉族人群中卡马西平导致SJS/TEN与HLA-B基因的相关性

目的:探讨中国南方汉族人群中卡马西平(CBZ)所致Stevens-Johnson综合征/中毒性表皮坏死松解症(SJS/TEN)与HLA-B基因的相关性。方法:采用病例对照研究,收集11例CBZ-SJS/TEN患者(CBZ-SJS/TEN组)、93例CBZ耐受患者(CBZ耐受组)及93例未服用抗癫痫药物的正常人(正常对照组)。PCR和测序法检测其HLA-B*1502基因型;χ2检验分析HLA-B*1502及其他HLA-B位点与CBZ-SJS/TEN的相关性。结果:CBZ-SJS/TEN组的HLA-B*1502基因阳性率为72.7%,显著高于CBZ耐受组及正常对照组。3例HLA-B*1502阴性CBZ-SJS/TEN患者的基因型分别为HLA-B*1511/1511、5401/5401及4001/4601。除HLA-B*1502之外,HLA-B*1511基因频率在CBZ-SJS/TEN患者与中国南方汉族正常人群之间具有显著的统计学差异,其他位点差异均无显著性。结论:在我国南方汉族人群中HLA-B*1502与CBZ-SJS/TEN具有相关性,建议汉族人群在服用CBZ前应该进行基因型检测。同时,对HLA-B*1502阴性个体使用CBZ治疗时,需密切监视,避免SJS/TEN的出现。

Correlation between the carbamazepine induced Stevens-Johnson syndrome/toxic epidermal necrolysis and HLA-B gene in southern Han Chinese

Objective To explore the correlation between carbamazepine(CBZ) induced Stevens-Johnson syndrome /toxic epidermal necrolysis(SJS/TEN) and HLA-B gene in southern Han Chinese.Methods Samples from 11 patients with CBZ-induced SJS/TEN(CBZ-SJS/TEN group),93 CBZ-tolerant patients(CBZ-tolerant group),and 93 normal subjects as controls(control group) were collected,all the patients were southern Han Chinese.HLA-B genotype was detected by polymerase chain reaction with sequence specific primers(PCR-SSP) and sequencing.Results The positive rate of HLA-B*1502 gene in CBZ-SJS/TEN group was 72.7%,which was significantly higher than those in CBZ-tolerant group and control group.The genotypes of the 3 HLA-B*1502 gene negative patients were HLA-B*1511/1511,5401/5401,and 4001/4601,respectively.Except HLA-B*1502 and HLA-B*1511,there was no significant difference in the frequency of the other HLA-B alleles between CBZ-SJS/TEN patients and normal southern Han Chinese.Conclusions There existed the association between HLA-B*1502 and CBZ-induced SJS/TEN,genotype testing before initiating CBZ therapy is suggested in Han Chinese.Furthermore,physicians should also be vigilant about SJS/TEN in those with negative HLA-B*1502.