Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.
Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.
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DOI：
10.1038/clpt.2010.250
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发表时间：
2011-01
影响因子：
6.7
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中科院分区：
文献类型：
--
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重性抑郁障碍（MDD）是一种常见的精神疾病。选择性5-羟色胺再摄取抑制剂（SSRIs）是用于治疗MDD的一类重要药物。然而，许多患者对SSRI治疗没有充分反应。我们使用药物代谢组学为基础的药物基因组学研究策略来确定西酞普兰/艾司西酞普兰治疗结局生物标志物。20例艾司西酞普兰缓解者和20例非缓解者血浆样本的代谢组学分析显示，甘氨酸与治疗结局呈负相关（p=0.0054）。通过使用来自SSRI治疗的MDD患者的529个DNA样本对编码甘氨酸合成和降解酶的基因的标签单核苷酸多态性（SNP）进行基因分型来进行观察。甘氨酸脱氢酶基因中的rs 10975641 SNP与治疗结果表型相关。然后对Rs 10975641进行基因分型，在星星 *D抑郁症研究的1245例MDD患者的DNA中，Rs 10975641具有显著性（p=0.02）。这些结果突出了甘氨酸在SSRI反应中的可能作用和药物代谢组学用于“告知”药物基因组学。
Major depressive disorder (MDD) is a common psychiatric disease. Selective serotonin reuptake inhibitors (SSRIs) are an important class of drugs used to treat MDD. However, many patients do not respond adequately to SSRI therapy. We used a pharmacometabolomics-informed pharmacogenomic research strategy to identify citalopram/escitalopram treatment outcome biomarkers. Metabolomic assay of plasma samples from 20 escitalopram remitters and 20 non-remitters showed that glycine was negatively associated with treatment outcome (p=0.0054). That observation was pursued by genotyping tag single nucleotide polymorphisms (SNPs) for genes encoding glycine synthesis and degradation enzymes using 529 DNA samples from SSRI-treated MDD patients. The rs10975641 SNP in the glycine dehydrogenase gene was associated with treatment outcome phenotypes. Rs10975641 was then genotyped and was significant (p=0.02) in DNA from 1245 MDD patients in the STAR*D depression study. These results highlight both a possible role for glycine in SSRI response and the use of pharmacometabolomics to “inform” pharmacogenomics.
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影响因子：
11
作者：
Kato, M.;Serretti, A.
通讯作者：
Serretti, A.
影响因子：
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Keller, MB
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Barrett, JC;Fry, B;Daly, MJ
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Daly, MJ