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Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive–compulsive disorder

The Pharmacogenomics Journal volume 13, pages 470–475 (2013)Cite this article

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Abstract

Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive–compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39–4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

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Acknowledgements

Financial support was received from the Spanish Ministry of Health, Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias de la Seguridad Social (PI10/01753, PI10/01003, CIBER-CB06/03/0034), the Ministry of Science and Innovation, MICINN (SAF2008-00357), the ‘Centro de Investigación en Red en Epidemiología y Salud Pública’, CIBERESP (PI050960; PI000954; PI040632 and PI040619), the Department of Health and the Department of Universities Research and Information Society of the Generalitat de Catalunya (2009SGR1554). JL has received an Intensification of Research Activity grant (Programme I3SNS-INT 11/323) from the Instituto de Salud Carlos III (Spain) during 2012. ER was funded by the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). We thank all the study participants and staff from the Department of Psychiatry of the Hospital Universitari de Bellvitge who helped to obtain the study sample. We also thank Michael Maudsley for help with the English.

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Authors and Affiliations

  1. Neuroscience Group-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), CIBERSAM (Centro de Investigación en Red de Salud Mental-Instituto de Salud Carlos III), L'Hospitalet de Llobregat, Barcelona, Spain

    E Real, P Alonso, C Segalàs, C López-Solà & J M Menchón

  2. Department of Psychiatry, OCD Clinical and Research Unit, Bellvitge Hospital, Feixa Llarga s/n, L’Hospitalet de Llobregat, Barcelona, Spain

    E Real, P Alonso, C Segalàs, M Subirà, C López-Solà & J M Menchón

  3. Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), and CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain

    M Gratacòs, G Escaramís & X Estivill

  4. Hospital Psiquiàtric Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus, Spain

    J Labad

  5. Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain

    P Alonso & J M Menchón

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  1. E Real
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Real, E., Gratacòs, M., Labad, J. et al. Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive–compulsive disorder. Pharmacogenomics J 13, 470–475 (2013). https://doi.org/10.1038/tpj.2012.30

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