Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
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DOI：
10.1371/journal.pone.0001872
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发表时间：
2008-04-02
期刊：
影响因子：
3.7
通讯作者：
Hamilton SP
中科院分区：
文献类型：
--
作者：
Peters EJ;Slager SL;Kraft JB;Jenkins GD;Reinalda MS;McGrath PJ;Hamilton SP
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遗传多态性相关。我们采用两阶段病例对照研究设计，将来自缓解抑郁症序贯替代治疗（星星 *D）试验的1,953例受试者分为发现组（n = 831）和验证组（n = 1,046）。 对来自5个（CYP 2D 6、ABCB 1、CYP 2C 19、CYP 3A 4和CYP 3A 5）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系。在第二阶段中验证了在第一阶段中发现具有统计学显著性的那些多态性的显著关联。在这两个阶段，所检测的药代动力学基因中没有遗传多态性与我们的反应或耐受表型显著相关。为了管理西酞普兰的药物治疗，我们检查的常见药代动力学DNA变体的常规筛选似乎具有有限的临床实用性。
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. 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. 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.
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影响因子：
3.2
作者：
Gutierrez, MM;Rosenberg, J;Abramowitz, W
通讯作者：
Abramowitz, W
影响因子：
2.5
作者：
Reis, M;Lundmark, M;Bengtsson, F
通讯作者：
Bengtsson, F
影响因子：
3.4
作者：
De Leon, J;Armstrong, SC;Cozza, KL
通讯作者：
Cozza, KL
影响因子：
9.8
作者：
McMahon, FJ;Buervenich, S;Manji, H
通讯作者：
Manji, H
DOI：
10.1073/pnas.050585397
发表时间：
2000-03-28
影响因子：
11.1
作者：
Hoffmeyer, S;Burk, O;Brinkmann, U
通讯作者：
Brinkmann, U