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Combined effect of common gene variants on response to drug withdrawal therapy in medication overuse headache

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

No information is currently available on genetic determinants of short-term response to drug withdrawal in medication overuse headache (MOH). In the present study, we aimed to evaluate the role of 14 polymorphisms in 8 candidate genes potentially relevant for drug addiction (OPRM1, DRD2, DBH, COMT, BDNF, SLC6A4, 5HT2A, and SLC1A2) as predictors for detoxification outcome of MOH patients at 2 months of follow-up.

Methods

Genotyping was conducted by PCR, PCR-RFLP analysis, or real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. The association between gene variants and risk of unsuccessful detoxification was evaluated by univariate and multivariate logistic regression analyses.

Results

One hundred and eight MOH patients with effective drug withdrawal therapy and 65 MOH patients with unsuccessful detoxification were available for the analysis. In the multivariable logistic regression analysis, triptan overuse (odds ratio (OR) 0.271, 95 % confidence interval (CI) 0.083–0.890, P = 0.031) and TT genotype carriage of DRD2 NcoI (OR 0.115, 95 % CI 0.014–0.982, P = 0.048) emerged as independent predictors for unsuccessful detoxification. In addition, carriers of at least four of the six top-ranked gene variants (P < 0.10) were found at higher odds for unsuccessful detoxification than patients with ≤3 high-risk genotypes (OR 3.40, 95 % CI 1.65–7.01, P = 0.001).

Conclusion

This exploratory study suggests that DRD2 NcoI may be a genetic determinant of detoxification outcome in MOH patients. Our findings also show that an approach based on the combination of multiple genetic markers could be clinically useful for identification of MOH patients at higher risk for unsuccessful detoxification.

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Acknowledgments

This work was funded by grants from Regione Piemonte, Ricerca Sanitaria Finalizzata, to A.A.G. (2006) and to P.L.C. (2003, 2007, and 2008), from the Italian Ministry of Health (RC2010) to National Neurological Institute C. Mondino and from Fondazione della Comunità del Novarese. S.C. holds a PhD fellowship supported by the Compagnia di San Paolo.

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale “A. Avogadro”, Largo Donegani 2, 28100, Novara, Italy

    Sarah Cargnin, Pier Luigi Canonico, Armando A. Genazzani & Salvatore Terrazzino

  2. Headache Science Centre, C. Mondino National Neurological Institute, Pavia, Italy

    Michele Viana, Grazia Sances, Natascia Ghiotto, Cristina Tassorelli & Giuseppe Nappi

  3. Laboratory of Experimental Neurobiology, National Neurological Institute C. Mondino, Pavia, Italy

    Marika Bianchi

  4. Department of Brain and Behaviour, University of Pavia, Pavia, Italy

    Cristina Tassorelli

Authors
  1. Sarah Cargnin
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  2. Michele Viana
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  3. Grazia Sances
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  4. Marika Bianchi
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  5. Natascia Ghiotto
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  6. Cristina Tassorelli
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  9. Armando A. Genazzani
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  10. Salvatore Terrazzino
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Correspondence to Salvatore Terrazzino.

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Cargnin, S., Viana, M., Sances, G. et al. Combined effect of common gene variants on response to drug withdrawal therapy in medication overuse headache. Eur J Clin Pharmacol 70, 1195–1202 (2014). https://doi.org/10.1007/s00228-014-1726-6

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  • DOI: https://doi.org/10.1007/s00228-014-1726-6

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