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Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine

The Pharmacogenomics Journal volume 10, pages 126–133 (2010)Cite this article

Abstract

To identify genes that may be relevant to the molecular action of antidepressants, we investigated transcriptional changes induced by the selective serotonin reuptake inhibitor paroxetine in a serotonergic cell line. We examined gene expression changes after acute treatment with paroxetine and sought to validate microarray results by quantitative PCR (qPCR). Concordant transcriptional changes were confirmed for 14 genes by qPCR and five of these, including the adrenomedullin gene (Adm), either approached or reached statistical significance. Reporter gene assays showed that a SNP (rs11042725) in the upstream flanking region of ADM significantly altered expression. Association analysis demonstrated rs11042725 to be significantly associated with response to paroxetine (odds ratio=0.075, P<0.001) but not with response to either fluoxetine or citalopram. Our results suggest that ADM is involved with the therapeutic efficacy of paroxetine, which may have pharmacogenetic utility.

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Acknowledgements

This research was supported by the Health Research Council of NZ and University of Otago. RN46A cells were a kind gift from Scott Whittemore, Laboratory of Molecular Neurobiology, Louisville, Kentucky, USA. Genotyping data were formatted into Paradox by Sarah Rowe, Department of Psychological Medicine, University of Otago, Christchurch.

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Authors and Affiliations

  1. Department of Pathology, Gene Structure & Function Laboratory, University of Otago, Christchurch, New Zealand

    D M Glubb, P C McHugh, X Deng & M A Kennedy

  2. Department of Psychological Medicine, University of Otago, Christchurch, New Zealand

    P R Joyce

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  1. D M Glubb
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  2. P C McHugh
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  3. X Deng
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Correspondence to D M Glubb.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Glubb, D., McHugh, P., Deng, X. et al. Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine. Pharmacogenomics J 10, 126–133 (2010). https://doi.org/10.1038/tpj.2009.33

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