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  

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

作　　者：吴培培[1] 李奕[1] 杨飞[2] 乔海灵[1] 杨静[1] 

机构地区：[1]郑州大学临床药理研究所,河南郑州450052 [2]郑州大学第一附属医院急诊科,河南郑州450052

出　　处：《中国药理学通报》2013年第1期113-117,共5页Chinese Pharmacological Bulletin

基　　金：河南省科技创新杰出青年基金(No 104100510008);河南省青年骨干教师资助项目[No教高(2012)704]

摘　　要：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。Aim To explore the association between cutaneous adverse drug reactions（cADR） and HLA ge- netic polymorphisms in patients with drug eruption, in order to provide basis for guarding and treating drug e- ruptions. Methods Forty-eight patients with drug-in- duced 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 andHLA-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 ）. Con- clusions 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.

关 键 词：药疹 基因多态性 抗癫痫药物 HLA PCR-SSP RT—PCR 

分 类 号：R392.11[医药卫生—免疫学] R394.2[医药卫生—基础医学]