HLA-A、B基因型与卡马西平、奥卡西平致斑丘疹的相关性分析  

Association analysis between HLA-A/B alleles and maculopapular exanthema induced by carbamazepine or oxcarbazepine

作　　者：何娜[1] 宋旺 刘晓蓉[1] 黎冰梅[1] 石奕武[1] HE Na;SONG Wang;LIU Xiaorong;LI Bingmei;SHI Yiwu(Department of Neurology,the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China)

机构地区：[1]广州医科大学附属第二医院神经内科癫痫专科,广州510260

出　　处：《癫痫杂志》2022年第2期108-115,共8页Journal of Epilepsy

基　　金：广州市卫生健康科技项目(20191A011076);中国抗癫痫协会癫痫科研基金UCB基金(2020006B)。

摘　　要：目的 分析HLA-A、B基因型与卡马西平(Carbamazepine,CBZ)和奥卡西平(Oxcarbazepine,OXC)致斑丘疹的相关性,探寻两者致斑丘疹的遗传危险因素。方法 回顾性分析广州医科大学附属第二医院癫痫专科2016年1月—2021年10月服用CBZ或OXC后出现轻度斑丘疹的患者(皮疹组)和耐受患者(非皮疹组),抽提外周血DNA,运用高分辨率测序方法对HLA-A和HLA-B等位基因进行测序分型,通过病例对照研究比较二者所致斑丘疹与HLA基因型的相关性。结果 共收集到100例CBZ皮疹患者、100例CBZ非皮疹患者、50例OXC皮疹患者和50例OXC非皮疹患者。CBZ、OXC皮疹组与非皮疹组在年龄、性别方面均无统计学差异。CBZ皮疹组平均潜伏期为(11.31±11.00)d,平均过敏剂量为(348.46±174.10)mg;OXC皮疹组平均潜伏期为(11.67±10.34)d,平均过敏剂量为(433.52±209.22)mg[相当于CBZ (289.01±139.48) mg],CBZ与OXC在潜伏期、过敏剂量比较无统计学差异(P>0.05)。HLA-A*24:02和A*30:01在CBZ皮疹组阳性率分别为28%和6%,明显高于CBZ非皮疹组(16%和0%),均具有统计学差异(P值均为0.04);HLA-B*40:01在CBZ皮疹组阳性率为18%,明显低于CBZ非皮疹组(40%),具有统计学差异(P<0.001)。尚未发现HLA-A或B基因型与OXC皮疹有相关性。将CBZ和OXC所致皮疹汇总后,综合分析,仍发现HLA-A*24:02和A*30:01在皮疹组阳性率高于非皮疹组,HLA-B*40:01阳性率低于非皮疹组,差异均具有统计学意义。结论 HLA-A*24:02和A*30:01与CBZ导致的斑丘疹有关,可能是芳香族抗癫痫药物的通用危险因素。Objective To analyze the correlation between HLA-A and B genotypes and maculopapular exanthema(MPE) caused by Carbamazepine(CBZ) and Oxcarbazepine(OXC),and to explore the genetic risk factors of MPE.Methods Patients with MPE(rash group) and patients without MPE(non-rash group) after taking CBZ or OXC were retrospectively collected from January 2016 to October 2021 in the Second Affiliated Hospital of Guangzhou Medical University.DNA was extracted from peripheral blood.HLA-A and HLA-B alleles were sequenced by high resolution sequencing,and a case-control study was conducted to analysis the correlations between MPE and HLA genotypes.Results A total of 100 patients with CBZ-MPE,100 patients with CBZ-tolerant,50 patients with OXC-MPE,and 50patients with OXC-tolerant were collected.There was no significant difference in age and sex between CBZ,OXC rash groups and non-rash groups The average latency of CBZ-rash group was(11.31±11.00) days and their average dosage was(348.46±174.10) mg;the average latency of OXC-rash group was(11.67±10.34) days and their average dosage was(433.52±209.22) mg [equivalent to CBZ(289.01±139.48 mg)],showing no significant difference in latency and dosage between CBZ and OXC(P>0.05).The positive rates of HLA-A*24:02 and A*30:01 in CBZ-rash group were 28% and 6%,respectively,which were significantly higher than those in CBZ-non rash group(16% and 0%,both P=0.04).The positive rate of HLA-B*40:01 in CBZ-rash group was 18%,which was significantly lower than that in CBZ-non rash group(40%,P<0.001).No association between HLA-A or B genotype and OXC-rash was found yet.When pooled,it was still found that the positive rates of HLA-A*24:02 and A*30:01 in the rash group were higher than those in the non-rash group,while the positive rate of HLA-B*40:01 in the rash group was lower than that in the non-rash group,and the difference was statistically significant(P<0.05).Conclusions HLA-A*24:02 and A*30:01 were associated with MPE caused by CBZ,and may be common risk factors for aromatic antiepileptic

关 键 词：卡马西平 奥卡西平 斑丘疹 遗传危险因素 

分 类 号：R758.25[医药卫生—皮肤病学与性病学]