Adrenomedullin gene (ADM) and response to paroxetine

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Original Article

The Pharmacogenomics Journal advance online publication 28 July 2009; doi: 10.1038/tpj.2009.33

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

D M Glubb 1, P C McHugh 1, X Deng 1, P R Joyce 2 and M A Kennedy 1

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

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

Correspondence: Dr DM Glubb, Department of Pathology, Gene Structure & Function Laboratory, University of Otago, Christchurch P.O. Box 4345, Christchurch 8140, New Zealand. E-mail: dylan.glubb@otago.ac.nz

Received 17 February 2009; Revised 8 May 2009; Accepted 25 June 2009; Published online 28 July 2009.

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 ADMsignificantly altered expression. Association analysis demonstrated rs11042725 to be significantly associated with response to paroxetine (odds ratio=0.075, P<0.001)>ADM is involved with the therapeutic efficacy of paroxetine, which may have pharmacogenetic utility.