抗癫痫药物等引发药疹与人类白细胞抗原基因的相关性研究

目的探讨抗癫痫药物等引发药疹与HLA基因多态性的相关性,以期为药疹的预防和治疗提供依据。方法收集48例药疹患者,采用PCR-SSP方法检测HLA-B*1502、HLA-A*0206、HLA-A*3101、HLA-A*1101、HLA-B*5901、HLA-Cw*0704、HLA-Cw*0801、HLA-DRB1*1202等8个等位基因。采用RT-PCR检测HLA-B*1502基因阳性者中mRNA表达水平。结果药物引发的药疹可能与HLA-B*1502、HLA-Cw*0801、HLA-A*0206和HLA-Cw*0704等位基因相关(P<0.05);其中抗癫痫药物引发的重症药疹与HLA-B*1502等位基因的相关性最强(P<0.01);且抗癫痫药物引发的重症药疹HLA-B*1502 mRNA的表达水平明显高于耐受组及对照组(P<0.01)。结论抗癫痫药物引发的重症药疹与HLA-B*1502等位基因密切相关。HLA-B*1502mRNA表达水平可以作为预测抗癫痫药物诱发重症药疹的重要指标。

Drug-induced cADR and polymorphism of HLA genes:A correlational study

Aim To explore the association between cutaneous adverse drug reactions(cADR) and HLA genetic polymorphisms in patients with drug eruption,in order to provide basis for guarding and treating drug eruptions.Methods Forty-eight patients with drug-induced cADR were enrolled to detect HLA-B*1502,HLA-A*0206,HLA-A*3101,HLA-A*1101,HLA-B*5901,HLA-Cw*0704,HLA-Cw*0801,HLA-DRB1*1202 alleles by polymerase chain reaction with sequence specific primers(PCR-SSP).The changes of HLA-B*1502 mRNA level were detected by relative fluorescence quantitative PCR(RT-PCR).Results HLA-B*1502,HLA-Cw*0801,HLA-A*0206 and HLA-Cw*0704 alleles might be associated with drug-induced cADR(P<0.05).Of which,HLA-B*1502 allele showed the highest relative risk for bullous drug cADR with SJS/TEN(P<0.01).Compared with control and AED-tolerant group respectively,the levels of HLA-B*1502 mRNA in AED-induced SJS/TEN group indicated a marked increase(P<0.01).Conclusions HLA-B*1502 allele is strongly associated with AED-induced SJS/TEN.Detection of HLA-B*1502 mRNA level can be the important indicator as prevention against AED-induced SJS/TEN.