Journal article
Changes in the peripheral blood gene expression profile induced by 3 Months of valproate treatment in patients with newly diagnosed epilepsy
Frontiers in Neurology, Vol.6
2015
Abstract
Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy. As a well-known histone deacetylase (HDAC) inhibitor, VPA regulates epigenetic programming by altering the expression of many genes. The aim of study was to analyze differences in gene expression profiles before and after the start of VPA treatment in patients with newly diagnosed epilepsy. RNA sequencing was used to compare whole-genome gene expression patterns of peripheral blood from nine patients with epilepsy before and 3 months after the start of treatment with VPA. Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1. Functional annotation and network analyses showed activation of only one genetic network (enrichment score = 30), which included genes for cardiovascular system development and function, cell morphology, and hematological system development and function. The finding of such a small number of differently expressed genes between before and after the start of treatment suggests a lack of HDAC inhibition in these patients, which could be explained by the relatively low doses of VPA that were used. In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes. Therefore, to minimize the potential side effects of HDAC inhibition, it is recommended that the lowest effective dose of VPA be used for treating epilepsy.
Details
- Title
- Changes in the peripheral blood gene expression profile induced by 3 Months of valproate treatment in patients with newly diagnosed epilepsy
- Authors/Creators
- A. Rakitin (Author/Creator) - University of TartuS. Kõks (Author/Creator) - University of TartuE. Reimann (Author/Creator) - University of TartuE. Prans (Author/Creator) - University of TartuS. Haldre (Author/Creator) - University of Tartu
- Publication Details
- Frontiers in Neurology, Vol.6
- Publisher
- Frontiers Media
- Identifiers
- 991005540305607891
- Copyright
- © 2015 The Austhors
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.222 Epilepsy & Seizures
- 1.222.143 Epilepsy Treatment
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Clinical Medicine