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A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C)

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

Previous studies have shown that a small fraction of patients with peripheral neuropathic pain experiences >50% pain relief during treatment with selective serotonin reuptake inhibitors (SSRIs), whereas most patients have no or only slight relief. The aim of this study was to investigate the association between polymorphisms in genes involved in the serotonergic pathway and the effect of escitalopram on peripheral neuropathic pain.

Methods

We genotyped 34 participants from a placebo-controlled trial of escitalopram in peripheral neuropathic pain for polymorphisms in five genes: the serotonin receptor 2A (HTR2A) gene, the serotonin receptor 2C (HTR2C) gene, the ABCB1 gene encoding for the P-glycoprotein, the CYP2C19 gene, and the serotonin transporter gene (SLC6A4).

Results

The SNP rs6318 (Cys23Ser) in the HTR2C gene showed significant association with treatment response in men (p = 0.047), with 75% carrying the C allele being responders. The same tendency was seen in women. Similarly, carriership of the C allele at rs6318 was associated with better pain relief during treatment with escitalopram [odds ratio (OR) 15.5, p = 0.014)] Furthermore, there was a tendency of better relief with increasing number of short alleles for the 5-HTTLPR polymorphism of the serotonin transporter (OR 5.7, p = 0.057). None of the other polymorphisms showed a significant association with treatment response to escitalopram.

Conclusion

This study indicates that variation in the HTR2C gene is associated to the pain-relieving effect of escitalopram in patients with painful polyneuropathy.

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Acknowledgement

The authors thank research nurses M. Sørensen and R. Mitzi Henriksen for collecting blood samples, and lab technician P. Jordan for skillful technical work. We declare no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, Denmark

    Charlotte Brasch-Andersen, Malik U. Møller & Kim Brøsen

  2. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark

    Charlotte Brasch-Andersen & Lene Christiansen

  3. Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark

    Lene Christiansen & Mikael Thinggaard

  4. Department of Neurology, Odense University Hospital, Odense, Denmark

    Marit Otto & Søren H. Sindrup

  5. Department of Neurophysiology, Aarhus University Hospital, Aarhus, Denmark

    Marit Otto

  6. Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark

    Kim Brøsen

Authors
  1. Charlotte Brasch-Andersen
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  2. Malik U. Møller
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  3. Lene Christiansen
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  4. Mikael Thinggaard
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  5. Marit Otto
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  6. Kim Brøsen
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  7. Søren H. Sindrup
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Correspondence to Charlotte Brasch-Andersen.

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Brasch-Andersen, C., Møller, M.U., Christiansen, L. et al. A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C). Eur J Clin Pharmacol 67, 1131–1137 (2011). https://doi.org/10.1007/s00228-011-1056-x

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  • DOI: https://doi.org/10.1007/s00228-011-1056-x

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