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Rakitin A, Kõks S, Reimann E, et al. Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy. Front Neurol. 2015;6:188doi: 10.3389/fneur.2015.00188.
Rakitin, A., Kõks, S., Reimann, E., Prans, E., & Haldre, S. (2015). Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy. Frontiers in neurology, 6188. https://doi.org/10.3389/fneur.2015.00188
Rakitin, Aleksei, et al. "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): 188. doi: https://doi.org/10.3389/fneur.2015.00188
Rakitin A, Kõks S, Reimann E, Prans E, Haldre S. Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy. Front Neurol. 2015 Aug 31;6:188. doi: 10.3389/fneur.2015.00188. eCollection 2015. PMID: 26379622; PMCID: PMC4553897.
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Front Neurol. 2015 Aug 31;6:188. doi: 10.3389/fneur.2015.00188. eCollection 2015.

Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy.

Frontiers in neurology

Aleksei Rakitin, Sulev Kõks, Ene Reimann, Ele Prans, Sulev Haldre

Affiliations

  1. Department of Neurology and Neurosurgery, University of Tartu , Tartu , Estonia ; Neurology Clinic, Tartu University Hospital , Tartu , Estonia.
  2. Department of Pathophysiology, University of Tartu , Tartu , Estonia ; Centre of Translational Medicine, University of Tartu , Tartu , Estonia.

PMID: 26379622 PMCID: PMC4553897 DOI: 10.3389/fneur.2015.00188

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.

Keywords: epilepsy; gene expression; teratogenicity; valproate; valproic acid

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