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

Glubb, D M, McHugh, Patrick C, Deng, X, Joyce, P R and Kennedy, M A (2010) Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine. The Pharmacogenomics Journal, 10 (2). pp. 126-133. ISSN 1470-269X

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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

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Sharon Beastall
Date Deposited: 26 Jan 2012 11:16
Last Modified: 28 Aug 2021 11:14


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