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在一小部分中国癫痫患者样本中,左乙拉西坦引起的皮肤药物不良反应与HLA基因无关。

Levetiracetam-induced cutaneous adverse drug reactions were not associated with HLA genes in a small sample of Chinese patients with epilepsy.

作者信息

Hu Fa-Yun, Wang Wei, Ren Jie-Chuan, An Dong-Mei, Chen Jia-Ni, Zhou Dong

机构信息

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

出版信息

Epilepsy Res. 2016 Aug;124:12-5. doi: 10.1016/j.eplepsyres.2016.04.008. Epub 2016 May 2.

Abstract

PURPOSE

This study aimed to evaluate the clinical characteristics of levetiracetam (LEV)-induced cutaneous adverse drug reactions (cADRs) and to explore its possible genetic association with the human leukocyte antigen (HLA) genes.

METHODS

Nine cases with LEV-induced cADRs were recruited. Demographic and clinical information of these cases was summarized. Additionally, cases were matched with LEV-tolerant controls (1:4). High-resolution HLA class I and class II genotyping was performed for each participant. The allele frequencies between the cases and controls were compared.

RESULTS

All LEV-induced cADRs were mild skin rashes which occurred within 28 days of LEV exposure. The mean latency from LEV exposure to skin rash was (15.67±5.41) days (ranging 6-27). The carrier rates of the two alleles, HLA-DRB10405 and HLA-DQB10401, were higher in cases compared with controls (the same P=0.036, OR=13.875, 95% CI: 1.273-151.230). The association between the HLA-C*0304 allele and LEV-induced cADRs was boundary (P=0.05, OR=5.2, 95% CI: 1.086-24.897). However, the above-mentioned HLA alleles didn't reach statistical significance after multiple comparisons.

CONCLUSIONS

Safety monitoring was necessary within four weeks after the initiation of LEV treatment, although it has been regarded as a safe antiepileptic drug. Our study failed to show any potential link between HLA alleles and LEV-induced cADRs in Han Chinese. Further studies are needed to clarify the genetic and immunological mechanisms of LEV-induced cADRs.

摘要

目的

本研究旨在评估左乙拉西坦(LEV)所致皮肤不良反应(cADRs)的临床特征,并探讨其与人类白细胞抗原(HLA)基因的可能遗传关联。

方法

招募9例LEV所致cADRs患者。总结这些患者的人口统计学和临床信息。此外,将患者与耐受LEV的对照者按1:4进行匹配。对每位参与者进行高分辨率HLA I类和II类基因分型。比较患者和对照者之间的等位基因频率。

结果

所有LEV所致cADRs均为轻度皮疹,发生于LEV暴露后28天内。从LEV暴露至出现皮疹的平均潜伏期为(15.67±5.41)天(范围6 - 27天)。与对照者相比,患者中两个等位基因HLA - DRB10405和HLA - DQB10401的携带率更高(P均 = 0.036,OR = 13.875,95%CI:1.273 - 151.230)。HLA - C*0304等位基因与LEV所致cADRs之间的关联接近临界值(P = 0.05,OR = 5.2,95%CI:1.086 - 24.897)。然而,经过多重比较后,上述HLA等位基因未达到统计学意义。

结论

尽管LEV被认为是一种安全的抗癫痫药物,但在开始LEV治疗后的四周内进行安全监测是必要的。我们的研究未能显示HLA等位基因与汉族人群中LEV所致cADRs之间存在任何潜在联系。需要进一步研究以阐明LEV所致cADRs的遗传和免疫机制。

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