Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine.
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.
Glubb
D M
DM
Gene Structure & Function Laboratory, Department of Pathology, University of Otago, Christchurch, New Zealand. dylan.glubb@otago.ac.nz
McHugh
P C
PC
Deng
X
X
Joyce
P R
PR
Kennedy
M A
MA
D053607:Adrenomedullin / Q000235:genetics*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D002460:Cell Line; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D017374:Paroxetine / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects; D051381:Rats
C507862:ADM protein, human; D000928:Antidepressive Agents; D053607:Adrenomedullin; D017374:Paroxetine