抗癫痫药物皮肤不良反应与HLA-B*1502基因的相关性研究

摘要

目的：探讨江西省汉族人群中芳香族抗癫痫药物所致皮肤不良反应与HLA-B*1502基因的相关性。方法：采用病例对照研究，一共收集样本46例，其中Stevens-Johnson综合征（SJS）组13例，轻微皮肤反应（MPE）组19例，对照组（包括耐受者和正常志愿者）14例。采用序列特异性引物聚合酶链反应（SSP-PCR）技术检测HLA-B*1502的基因型。采用Fisher确切概率法检验分析HLA-B*1502与抗癫痫药物皮肤不良反应的相关性。结果：HLA-B*1502基因频率分别为SJS组100%（13/13），MPE组10.5%（2/19），对照组7.1%（1/14）。SJS组分别与MPE组和对照组比较差异具有统计学意义（P<0.05），MPE组与对照组比较差异无统计学意义（P<0.05）。结论：江西汉族人群中芳香族AEDs导致的SJS与HLA-B*1502基因具有强相关性，而MPE与之无相关性。建议江西汉族人群在采用AEDs治疗前应该进行HLA-B*1502基因型检测，阳性者应避免服用芳香族AEDs，此外还需警惕阴性者发生SJS等严重皮肤不良反应。%Objective:To investigate the correlation between the aromatic antiepileptic drugs(AEDs)induced cutaneous adverse drug reactions(cADRs)and HLA-B*1502 gene in Han population of Jiangxi province. Method:The case-control study was taken,A total of 46 cases of samples were collected,including 13 patients with Stevens-Johnson syndrome(SJS)(SJS group),19 patients with mild skin reaction(MPE)(MPE group),and 14 tolerance and normal volunteers as controls(control group).The sequence-specific primers polymerase chain reaction(SSP-PCR)technique was used to detect HLA-B*1502 genotype. The Fisher’s exact test was used to analyze the correlation between HLA-B*1502 and AEDs-cADRs. Result:The gene frequencies of HLA-B*1502were 100%(13/13)in SJS group,10.5%(2/19)in MPE group and 7.1%(1/14)in the control group. There were significant differences in the SJS group compared with MPE group and the control group(P<0.05),there was no statistically significant difference between the MPE group and the control group(P>0.05). Conclusion:There is a strong correlation between HLA-B*1502 gene and the aromatic AEDs-induced SJS,but the correlation between HLA-B*1502 gene and MPE has not been found in Han population of Jiangxi province. HLA-B*1502 gene type testing before initiating AEDs therapy is suggested for Han population of Jiangxi province. Those with positive HLA-B*1502 should avoid taking aromatic AEDs. Furthermore,physicians should also be vigilant about SCR ,such as SJS ,in those with negative HLA-B*1502.