Statins' protective effects on focal epilepsy are independent of LDL-C

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Epilepsia Open Pub Date : 2025-03-07 DOI:10.1002/epi4.70008

Zhen Sun, Jing Zhang, Yulong Li, Miao Tuo, Limin Yu, Yun Wang, Yanping Sun

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Abstract

Objective

This study evaluates the potential protective effects of statins against epilepsy, focusing on their differential impacts on focal and generalized epilepsy. It investigates the role of statins through the HMGCR gene and associated low-density lipoprotein (LDL) cholesterol levels.

Methods

A two-sample Mendelian randomization (MR) and summary-data-based MR (SMR) approach were employed using genetic instruments from genome-wide association studies (GWASs) and expression quantitative trait loci (eQTLs). Subgroup analyses examined focal and generalized epilepsy, with sensitivity tests, including MR-Egger regression and MR-PRESSO, to assess horizontal pleiotropy and robustness.

Results

SMR analysis found no significant association between HMGCR expression and epilepsy risk across subtypes (p > 0.05). However, inverse-variance-weighted MR (IVW-MR) showed that elevated LDL cholesterol mediated by HMGCR was linked to an increased risk of focal epilepsy (OR = 1.251, 95% CI = 1.135–1.378). No such association was observed for generalized epilepsy. Statins showed promise in reducing post-stroke epilepsy risk, likely through anti-inflammatory and neuroprotective effects.

Significance

The findings suggest that statins' protective effects may be subtype-specific, particularly in post-stroke focal epilepsy. Further research is needed to elucidate underlying mechanisms and optimize their therapeutic potential in epilepsy management.

Plain Language Summary

Statins, drugs typically used to manage cholesterol, may also lower the risk of developing certain types of epilepsy, especially post-stroke focal epilepsy, by reducing inflammation and protecting brain cells. The research found no clear effect of statins on generalized epilepsy or epilepsy caused by other factors. These results could aid in creating better treatments for epilepsy in the future.

Abstract Image

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他汀类药物对局灶性癫痫的保护作用与LDL-C无关。

目的：本研究评估他汀类药物对癫痫的潜在保护作用，重点研究其对局灶性癫痫和全身性癫痫的不同作用。它通过HMGCR基因和相关的低密度脂蛋白（LDL）胆固醇水平研究他汀类药物的作用。方法：利用全基因组关联研究（GWASs）和表达数量性状位点（eqtl）的遗传仪器，采用双样本孟德尔随机化（MR）和基于汇总数据的随机化（SMR）方法。亚组分析检查局灶性和全局性癫痫，采用敏感性试验，包括MR-Egger回归和MR-PRESSO，以评估水平多效性和稳健性。结果：SMR分析发现不同亚型HMGCR表达与癫痫风险无显著相关性（p < 0.05）。然而，反方差加权MR （IVW-MR）显示，HMGCR介导的LDL胆固醇升高与局灶性癫痫风险增加有关（OR = 1.251, 95% CI = 1.135-1.378）。在全身性癫痫中没有观察到这种关联。他汀类药物显示出降低中风后癫痫风险的希望，可能是通过抗炎和神经保护作用。意义：研究结果表明，他汀类药物的保护作用可能是亚型特异性的，特别是在脑卒中后局灶性癫痫中。需要进一步研究阐明其潜在机制并优化其在癫痫管理中的治疗潜力。简单的语言总结：他汀类药物通常用于控制胆固醇，也可以通过减少炎症和保护脑细胞来降低患某些类型癫痫的风险，特别是中风后局灶性癫痫。研究发现他汀类药物对全身性癫痫或其他因素引起的癫痫没有明显的疗效。这些结果可能有助于在未来创造更好的癫痫治疗方法。

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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