Association of serotonin transporter promoter (5-HTTLPR) and intron 2 (VNTR-2) polymorphisms with treatment response in temporal lobe epilepsy.
OBJECTIVE
Temporal lobe epilepsy (TLE) is the most common epilepsy and about 30% of patients have poorly controlled seizures. Neurobiology underlying responsiveness to medical treatment in TLE patients is unclear and there are currently no biological tests to predict course of the disease. Animal and human studies repeatedly suggested serotonergic dysfunction in subjects with TLE. We investigated association of serotonin transporter (5-HTT) gene polymorphisms with medical treatment response in patients with TLE.


METHODS
We analyzed 5-HTT gene linked polymorphic region (5-HTTLPR) in promoter and variable number of tandem repeats in the second intron of the 5-HTT gene (VNTR-2) in 101 consecutive subjects with TLE.


RESULTS
TLE patients with the combination of transcriptionally more efficient genotypes, i.e. 5-HTTLPR L/L and VNTR-2 12/12, had increased seizure refractoriness to antiepileptic medication therapy and shorter periods of seizure freedom, than subjects with other combinations of the 5-HTT genotypes. There were no other clinical or demographic differences among patient groups based on the 5-HTT genotypes.


CONCLUSIONS
Combination of the 5-HTT genotypes linked with higher 5-HTT gene expression was found to be associated with worse response to optimal drug therapy. Further studies should determine potential role of this 5-HTT genotype polymorphism in epileptogenesis.
Hecimovic
Hrvoje
H
Zagreb Epilepsy Center, Department of Neurology, University Hospital, Vinogradska 29, HR-10000 Zagreb, Croatia. Hecimovic@inet.hr
Stefulj
Jasminka
J
Cicin-Sain
Lipa
L
Demarin
Vida
V
Jernej
Branimir
B
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins