抗癫痫药物皮肤不良反应与HLA-B 1502基因关联性研究  

Association between cutaneous adverse reactions to antiepileptic drugs and HLA-B＊1502 allele

作　　者：高玫梅[1] 石奕武[1] 于美娟[1] 李雪莲[1] 王鹏[1] 刘晓蓉[1] 黎冰梅[1] 邓宇虹[1] 常好会[1] 廖卫平[1] 

机构地区：[1]广州医学院第二附属医院神经科学研究所基础部,广州510260

出　　处：《中华神经医学杂志》2009年第5期493-495,499,共4页Chinese Journal of Neuromedicine

基　　金：基金项目：广东省自然科学基金（5300988）;广州医学院第二附属医院基金（2007-5）

摘　　要：目的研究抗癫痫药物引致的皮肤不良反应和人白细胞抗原HLA-B＊1502基因的关联性，探讨抗癫痫药物的个体化治疗。方法广州医学院第二附属医院癫痫门诊自2007年1月至2008年5月共收治癫痫患者31例，其中应用卡马西平（CBZ）引致皮肤不良反应13例[Stevens-Johnson综合征（SJS）6例、轻度斑丘疹（MPE）7例]，无皮肤不良反应15例，应用拉莫三嗪fLTG）引致MPE3例。采用顺序特异性引物聚合酶链反应（PCR-SSP）检测以上患者和未服用过CBZ或LTG的30例正常对照者的月，J4-B＊1502基因分型。结果IILA—B＊1502基因型阳性例数和基因频率分别为：CBZ引致SJS组6例（6／6，100％），CBZ引致MPE组4例（4／7，57％），LTG引致MPE组1例（1／3，33％1．无皮肤不良反应组1例（1／15，7％），正常对照组3例（3／30，10％）。CBZ引致SJS组、CBZ引致MPE组患者HLA-B＊1502基因型阳性率均高于正常对照组和无皮肤不良反应组．差异均有统计学意义（P〈0．05）。结论CBZ导致的皮肤不良反应与HLA-B＊1502基因型有关。Objective To investigate the association between cutaneous adverse drug reactions （CADRs） caused by antiepileptic drugs and HLA -B＊1502 allele. Methods In 31 epileptic patients presented to the Epilepsy Clinic of the Second Affiliated Hospital of Guangzhou Medical College between January 2007 and May 2008, 13 had CADR to carbanazepine （CBZ） including 6 with Stevens-Johnson syndrome （SJS） and 7 with mild maculopapular exanthema （MPE）; 15 were CBZ-tolerant, and 3 had lamotrigine （LTG）-induced MPE. All the patients tmderwent examinations using polymerase chain reaction with sequence specific primers to analyze HLA -B＇1502 allele frequencies, with 30 healthy subjects without a history of using CBZ or LTG as the control. Results HLA -B＊1502 allele frequency was 100% （6/6） in patients with CBZ-SJS, 57% （4/7） in patients with CBZ-induced MPE, and 33 % （1/3） in patients with LTG-induced MPE. The frequency was 7% （1/15） in CBZ-tolerant patients and 10% （3/30） in the control subjects. Compared with the CBZ-tolerant patients and the control subjects, the patients with CBZ-induced SJS and MPE had significantly increased HLA -B＊1502 allele frequency （P〈0.05）. Conclusions HLA -B＊1502 allele is associated with CADRs to CBZ in epileptic patients.

关 键 词：人白细胞抗原HLA-B＊1502基因 抗癫痫药物 皮肤不良反应 

分 类 号：R686[医药卫生—骨科学]