Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
The Second Hospital of Jilin University, Changchun, China.
BMC Pharmacol Toxicol. 2024 Jan 2;25(1):1. doi: 10.1186/s40360-023-00718-2.
A connection between diabetes and an increased risk of epilepsy has been suggested by observational studies. Animal studies have also shown that antihyperglycemic drugs can improve seizures. However, it is unclear whether antihyperglycemic drugs have a causal role in epilepsy in humans. To investigate this potential causal relationship, a Mendelian randomisation study was conducted using International League Against Epilepsy data as the discovery set and FinnGen data as the replication set. It was discovered that three antidiabetic drug target genes, ETFDH, CYP21A2 and CYP2D6, were involved in the occurrence of epilepsy. In particular, ETFDH was identified as a target gene in both the discovery set (inverse variance weighting [IVW], odds ratio [OR] = 1.018, 95% confidence interval [CI], 1.004-1.033, p = 0.009) and replication set (IVW, OR = 1.074, 95% CI, 1.034-1.114, p = 0.00016), and CYP21A2 was identified in the discovery set (IVW, OR = 1.029, 95% CI, 1.005-1.053, p = 0.016) and replication set (IVW, OR = 1.057, 95% CI, 1.001-1.116, p = 0.045) as having a causal association with an increased risk of epilepsy. Conversely, the CYP2D6 gene was found to be a protective factor for epilepsy in both the discovery set (IVW, OR = 0.0984, 95% CI, 0.969-0.998, p = 0.025) and replication set (IVW, OR = 0.977, 95% CI, 0.955-1.000, p = 0.046). A search of DrugBank revealed that metformin, an anti-glucose drug, is an inhibitor of the ETFDH gene and may have a potential therapeutic effect on epilepsy.
一些观察性研究提示糖尿病与癫痫风险增加之间存在关联。动物研究还表明，抗高血糖药物可以改善癫痫发作。然而，抗高血糖药物是否在人类癫痫中起因果作用尚不清楚。为了研究这种潜在的因果关系，使用国际抗癫痫联盟数据作为发现集，芬兰遗传研究数据作为复制集，进行了孟德尔随机化研究。研究发现，三种抗糖尿病药物靶点基因 ETFDH、CYP21A2 和 CYP2D6 与癫痫的发生有关。特别是，ETFDH 被确定为发现集（逆方差加权 [IVW]，比值比 [OR] = 1.018，95%置信区间 [CI]，1.004-1.033，p = 0.009）和复制集（IVW，OR = 1.074，95%CI，1.034-1.114，p = 0.00016）中的目标基因，CYP21A2 被确定为发现集（IVW，OR = 1.029，95%CI，1.005-1.053，p = 0.016）和复制集（IVW，OR = 1.057，95%CI，1.001-1.116，p = 0.045）中与癫痫风险增加有因果关系。相反，CYP2D6 基因在发现集（IVW，OR = 0.0984，95%CI，0.969-0.998，p = 0.025）和复制集（IVW，OR = 0.977，95%CI，0.955-1.000，p = 0.046）中被发现是癫痫的保护因素。对 DrugBank 的检索显示，抗葡萄糖药物二甲双胍是 ETFDH 基因的抑制剂，可能对癫痫有潜在的治疗作用。
