The relationship between zinc and epilepsy

Abstract Background Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc, in relation to epileptic seizures, as well as explore the possible mechanisms by which zinc contributes to epilepsy. Methods First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on two-sample Mendelian randomization analysis. And then, Then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model and xgboot model. Results 1. There was a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044, p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003, p = 0.022, p = 0.009).2. A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e-2). MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e-5).3. The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 1.9e-4). Within 4 to 24 hours after experiencing epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e-5), compared to the rats without seizure. Conclusion The mechanism of the increased risk of epilepsy caused by zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.