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

Rakitin A, Kõks S, Reimann E, Prans E, Haldre S - Front Neurol (2015)

Bottom Line: Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy.Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1.In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosurgery, University of Tartu , Tartu , Estonia ; Neurology Clinic, Tartu University Hospital , Tartu , Estonia.

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.

No MeSH data available.


Related in: MedlinePlus

Annotation enrichment analysis. A network including the gene functions “cardiovascular system development and function,” “cell morphology,” and “hematological system development and function” was significantly enriched in patients with epilepsy after initiation of treatment with valproic acid [score = –log(p-value) = 30]. Red nodes designate up-regulated genes. Numbers indicate the log2 fold change (0 is equal expression). Uncolored nodes are genes in this network that were not in our list of differentially expressed genes.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4553897&req=5

Figure 1: Annotation enrichment analysis. A network including the gene functions “cardiovascular system development and function,” “cell morphology,” and “hematological system development and function” was significantly enriched in patients with epilepsy after initiation of treatment with valproic acid [score = –log(p-value) = 30]. Red nodes designate up-regulated genes. Numbers indicate the log2 fold change (0 is equal expression). Uncolored nodes are genes in this network that were not in our list of differentially expressed genes.

Mentions: Functional annotation of expression profiles was subsequently applied to identify functional changes in the context of genetic networks. A dataset containing 11 genes that had significant differential expression between before and after initiation of VPA treatment was uploaded into the Ingenuity Pathway Analysis software program. Only one genetic network was identified (enrichment score = 30), which included genes related to cardiovascular system development and function, cell morphology, as well as hematological system development and function (Table 3; Figure 1).


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

Rakitin A, Kõks S, Reimann E, Prans E, Haldre S - Front Neurol (2015)

Annotation enrichment analysis. A network including the gene functions “cardiovascular system development and function,” “cell morphology,” and “hematological system development and function” was significantly enriched in patients with epilepsy after initiation of treatment with valproic acid [score = –log(p-value) = 30]. Red nodes designate up-regulated genes. Numbers indicate the log2 fold change (0 is equal expression). Uncolored nodes are genes in this network that were not in our list of differentially expressed genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553897&req=5

Figure 1: Annotation enrichment analysis. A network including the gene functions “cardiovascular system development and function,” “cell morphology,” and “hematological system development and function” was significantly enriched in patients with epilepsy after initiation of treatment with valproic acid [score = –log(p-value) = 30]. Red nodes designate up-regulated genes. Numbers indicate the log2 fold change (0 is equal expression). Uncolored nodes are genes in this network that were not in our list of differentially expressed genes.
Mentions: Functional annotation of expression profiles was subsequently applied to identify functional changes in the context of genetic networks. A dataset containing 11 genes that had significant differential expression between before and after initiation of VPA treatment was uploaded into the Ingenuity Pathway Analysis software program. Only one genetic network was identified (enrichment score = 30), which included genes related to cardiovascular system development and function, cell morphology, as well as hematological system development and function (Table 3; Figure 1).

Bottom Line: Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy.Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1.In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosurgery, University of Tartu , Tartu , Estonia ; Neurology Clinic, Tartu University Hospital , Tartu , Estonia.

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.

No MeSH data available.


Related in: MedlinePlus