Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Department of Neurosciences, CHUM Research Center, University of Montreal, Montreal, H2X 0A9, Canada.
Pharmacogenomics. 2020 Apr;21(5):325-335. doi: 10.2217/pgs-2019-0179. Epub 2020 Apr 20.
Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
药物抵抗是癫痫治疗的主要负担。我们旨在确定与特定抗癫痫药物（AEDs）反应相关的遗传生物标志物，用于治疗遗传全面性癫痫（GGE）。我们对 893 名对拉莫三嗪、左乙拉西坦和丙戊酸有反应或无反应的 GGE 患者进行了全基因组关联研究（GWAS），共涉及 330 万个常染色体单核苷酸多态性（SNP）。我们对 AED 反应的 GWAS 显示了 29 个基因组位点的关联有提示性证据（p <10），但没有显著的关联，这反映了其有限的效力。这些提示性关联突出了候选基因，这些基因与癫痫发生和神经发育有关。这是对 GGE 中 AED 反应的首次 GWAS，为即将进行的药物遗传学研究中的假设驱动候选基因分析提供了 SNP 关联的综合参考。
