Epilepsy Research
Volume 91, Issue 1 , Pages 35-38, September 2010

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

  • Hecimovic Hrvoje

      Affiliations

    • Zagreb Epilepsy Center, Department of Neurology, University Hospital, Vinogradska 29, HR-10000 Zagreb, Croatia
    • Corresponding Author InformationCorresponding author. Tel.: +385 1 3787731; fax: +385 1 3787731.
    • ,
  • Stefulj Jasminka

      Affiliations

    • Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia
    • ,
  • Cicin-Sain Lipa

      Affiliations

    • Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia
    • ,
  • Demarin Vida

      Affiliations

    • Zagreb Epilepsy Center, Department of Neurology, University Hospital, Vinogradska 29, HR-10000 Zagreb, Croatia
    • ,
  • Jernej Branimir

      Affiliations

    • Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia
    • Deceased.

Received 8 March 2010; received in revised form 25 May 2010; accepted 20 June 2010.

Summary 

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.

Keywords: Temporal lobe epilepsy, Serotonin, 5-HTTLPR, VNTR-2, Limbic system

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PII: S0920-1211(10)00155-5

doi:10.1016/j.eplepsyres.2010.06.008

Epilepsy Research
Volume 91, Issue 1 , Pages 35-38, September 2010

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