Causal Relationships Between Epilepsy, Anti-Epileptic Drugs, and Serum Vitamin D and Vitamin D Binding Protein: A Bidirectional and Drug Target Mendelian Randomization Study

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-12-20 DOI:10.1111/cns.70183

Zizhang Cheng, Jinyi Zuo, Xintao Peng, Haoran Zhang, Wenlong Su, Guoming Luan, Yuguang Guan

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Abstract

Aims

Previous studies suggest potential associations between epilepsy, anti-epileptic drugs (AEDs), and levels of vitamin D and vitamin D-binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods.

Methods

Using summary data from genome-wide association studies on serum 25-hydroxyvitamin D [25(OH)D] levels (N = 417,580), VDBP concentrations (N = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables. Additionally, eQTL data from eQTLGen (N = 31,684) were employed to model the effects of AEDs and evaluate their causal impact on both biomarkers.

Results

No causal relationships were found between serum 25(OH)D or VDBP levels and epilepsy. Although genetically predicted focal epilepsy risk was potentially associated with increased serum 25(OH)D levels (OR 1.031, 95% CI: 1.006–1.058, p = 0.017), and a higher genetic risk of juvenile myoclonic epilepsy was linked to lower VDBP levels (OR 0.977, 95% CI: 0.961–0.993, p = 0.004), both associations lost significance after multiple correction. Furthermore, significant associations were observed between serum 25(OH)D levels and AED target genes SCN4A, GABBR1, CA13, ALDH5A1, and CA8. No significant associations were found between AED target genes and VDBP levels after correction.

Conclusion

No causal relationships were found between genetically determined serum 25(OH)D levels, VDBP, and epilepsy or its subtypes. Furthermore, the use of AEDs, such as Carbamazepine, Oxcarbazepine, Progabide, and Valproic Acid, reduces serum 25(OH)D levels, while not affect VDBP levels.

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癫痫、抗癫痫药物与血清维生素D和维生素D结合蛋白之间的因果关系：一项双向和药物靶向孟德尔随机研究。

目的：先前的研究表明癫痫、抗癫痫药物（aed）和维生素D和维生素D结合蛋白（VDBP）水平之间存在潜在关联。本研究旨在利用孟德尔随机化（MR）方法探讨这些变量之间的因果关系。方法：利用血清25-羟基维生素D [25(OH)D]水平（N = 417,580）、VDBP浓度（N = 65,589）和不同类型癫痫（Ncases = 27,559）的全基因组关联研究汇总数据，进行MR分析，以确定这些变量之间的双向因果关系。此外，采用来自eQTLGen （N = 31,684）的eQTL数据来模拟aed的影响，并评估其对两种生物标志物的因果影响。结果：血清25(OH)D或VDBP水平与癫痫无因果关系。虽然遗传预测局灶性癫痫风险可能与血清25(OH)D水平升高相关（OR 1.031, 95% CI: 1.006-1.058, p = 0.017），青少年肌阵挛性癫痫较高的遗传风险与较低的VDBP水平相关（OR 0.977, 95% CI: 0.961-0.993, p = 0.004），但在多次校正后，这两种相关性都失去了显著性。此外，血清25(OH)D水平与AED靶基因SCN4A、GABBR1、CA13、ALDH5A1和CA8之间存在显著关联。校正后发现AED靶基因与VDBP水平无显著相关性。结论：基因测定的血清25(OH)D水平、VDBP与癫痫及其亚型之间没有因果关系。此外，使用卡马西平、奥卡西平、丙戊酸和丙戊酸等AEDs可降低血清25(OH)D水平，而不影响VDBP水平。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.