Epigenetic In Epilepsy

The epilepsies affect more than 65 million people worldwide and have a substantial missing heritability component.Epigenetics refers to heritable changes in gene expression beyond the DNA sequence or more broadly to processes that influence medium‐ to long‐term gene expression via effects on chromatin structure.Epigenet processes include DNA methylation, histone posttranslational modifications, and actions of certain noncoding RNAs. Epigenetic modifications present as excellent target candidates: genome-wide changes in gene expression are often observed in epileptic brain, and these broad gene expression changes may participate within a molecular network to result in epilepsy, with no single gene change by itself being critical. Also, acquired epilepsy develops following a latent period after a brain insult, potentially underpinned by the emergence of stable alterations to chromatin structure leading to enduring patterns of gene expression. Further, several recent studies detail the presence of epigenetic alterations in models of epilepsy and in humans, and there is evidence that manipulation of these can impact the epileptogenic process. Recently a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls,16 genome-wide significant loci, of which 11 are novel. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. The epigenetic mechanism may play a key role in interpreting how environmental factors cause the phenotype or phenotypic variations and how the DNA mutational variants may contribute to phenotypic traits. Interestingly status epilepticus produces alterations to all the major epigenetic processes. Experimental therapies targeting epigenetic processes have been reported to protect against prolonged seizures and epileptogenesis.The biochemical hallmarks of epigenetics can be detected in bio fluids and may have diagnostic potential.