Gene Structure & Function Laboratory, Department of Pathology, University of Otago, Christchurch, New Zealand.
Pharmacogenomics J. 2010 Apr;10(2):126-33. doi: 10.1038/tpj.2009.33. Epub 2009 Jul 28.
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.
为了确定可能与抗抑郁药的分子作用相关的基因，我们研究了选择性 5-羟色胺再摄取抑制剂帕罗西汀在 5-羟色胺能细胞系中诱导的转录变化。我们在帕罗西汀的急性治疗后检查了基因表达的变化，并通过定量 PCR(qPCR) 寻求验证微阵列结果。qPCR 确认了 14 个基因的一致转录变化，其中包括肾上腺髓质素基因(Adm)，其中 5 个基因接近或达到统计学意义。报告基因分析表明，ADM 上游侧翼区域的 SNP(rs11042725) 显著改变了表达。关联分析表明，rs11042725 与帕罗西汀的反应显著相关（优势比=0.075，P<0.001），但与氟西汀或西酞普兰的反应无关。我们的结果表明，ADM 参与了帕罗西汀的治疗效果，这可能具有药理学遗传的效用。
