在STAR*D研究样本中，药代动力学基因不影响对西酞普兰的反应或耐受性。
Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
作者信息
Peters Eric J, Slager Susan L, Kraft Jeffrey B, Jenkins Greg D, Reinalda Megan S, McGrath Patrick J, Hamilton Steven P
机构信息
Department of Psychiatry and Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
出版信息
PLoS One. 2008 Apr 2;3(4):e1872. doi: 10.1371/journal.pone.0001872.
BACKGROUND
We sought to determine whether clinical response or tolerance to the Selective Serotonin Reuptake Inhibitor (SSRI) citalopram is associated with genetic polymorphisms in potentially relevant pharmacokinetic enzymes.
METHODOLOGY
We used a two-stage case-control study design in which we split the sample of 1,953 subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial into a discovery (n = 831) and validation set (n = 1,046). Fifteen polymorphisms from five (CYP2D6, ABCB1, CYP2C19, CYP3A4, and CYP3A5) pharmacokinetic genes were genotyped. We examined the associations between these polymorphisms and citalopram response and tolerance. Significant associations were validated in the second stage for those polymorphism found to be statistically significant in the first stage.
CONCLUSIONS
No genetic polymorphism in the pharmacokinetic genes examined was significantly associated with our response or tolerance phenotypes in both stages. For managing pharmacological treatment with citalopram, routine screening of the common pharmacokinetic DNA variants that we examined appears to be of limited clinical utility.
背景
我们试图确定对选择性5-羟色胺再摄取抑制剂（SSRI）西酞普兰的临床反应或耐受性是否与潜在相关药代动力学酶的基因多态性有关。
方法
我们采用两阶段病例对照研究设计，将来自缓解抑郁的序贯治疗替代方案（STAR*D）试验的1953名受试者样本分为发现组（n = 831）和验证组（n = 1046）。对五个（CYP2D6、ABCB1、CYP2C19、CYP3A4和CYP3A5）药代动力学基因的15个多态性进行基因分型。我们研究了这些多态性与西酞普兰反应和耐受性之间的关联。在第一阶段发现具有统计学意义的那些多态性，在第二阶段进行了验证。
结论
在两个阶段中，所检测的药代动力学基因中的基因多态性均与我们的反应或耐受性表型无显著关联。对于西酞普兰的药物治疗管理，对我们所检测的常见药代动力学DNA变异进行常规筛查似乎临床效用有限。
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