Valproic acid blood genomic expression patterns in children with epilepsy - a pilot study.
OBJECTIVE
Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy.


METHODS
Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients).


RESULTS
The expression of 461 genes was altered in VPA patients (n = 11) compared with drug free patients (n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy (n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures (n = 3) and drug free seizure patients (n = 7).


CONCLUSIONS
VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity.
Tang
Y
Y
Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Glauser
T A
TA
Gilbert
D L
DL
Hershey
A D
AD
Privitera
M D
MD
Ficker
D M
DM
Szaflarski
J P
JP
Sharp
F R
FR
D000293:Adolescent; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics*; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D014635:Valproic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000927:Anticonvulsants; D004272:DNA, Mitochondrial; D002220:Carbamazepine; D014635:Valproic Acid; D017346:Protein Serine-Threonine Kinases