Association of serotonin transporter promoter (5-HTTLPR) and intron 2 (VNTR-2) polymorphisms with treatment response in temporal lobe epilepsy

Epilepsy Res. 2010 Sep;91(1):35-8. doi: 10.1016/j.eplepsyres.2010.06.008. Epub 2010 Jul 23.

Abstract

Purpose: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / therapeutic use
  • Epilepsy, Temporal Lobe / drug therapy*
  • Epilepsy, Temporal Lobe / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Introns / genetics*
  • Male
  • Middle Aged
  • Minisatellite Repeats / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Anticonvulsants
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins