Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study
Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study
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DOI：
10.1159/000319361
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发表时间：
2010-07
影响因子：
3.2
通讯作者：
P. Menu;F. Gressier;C. Verstuyft;P. Hardy;L. Becquemont;E. Corruble
中科院分区：
文献类型：
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作者：
P. Menu;F. Gressier;C. Verstuyft;P. Hardy;L. Becquemont;E. Corruble
简介：药物遗传学因素可以解释抑郁症患者对抗抑郁药反应的一些个体差异。我们重点关注 P-糖蛋白 (P-GP)，其表达取决于 ABCB1 基因（C3435T 变体：dbSNP：rs1045642）的功能多态性，3435CC 基因型与高水平的 P-GP 表达相关。 P-GP 作为血脑屏障的外排泵，可减少许多药物的细胞内渗透。关于 P-GP 与抗抑郁药反应之间的相互作用知之甚少。本研究的目的是评估 3435CC 基因型患者与 3435CT 和 3435TT 基因型患者相比，抗抑郁药物对抑郁症的反应是否有所不同。方法：117 名患有严重抑郁发作、需要新的抗抑郁药物治疗的住院患者参加了这项为期 4 周的前瞻性自然主义研究。使用汉密尔顿抑郁量表、贝克抑郁量表、临床医生总体印象改善和治疗指数以及体重变化来评估抗抑郁药物的反应。使用Taqman方法进行ABCB1基因分型。临床评估是根据基因型盲目进行的。结果：我们未能证明 3435 位 ABCB1 多态性对抗抑郁功效或耐受性有任何显着影响。讨论：虽然一些体外研究表明 P-GP 对抗抑郁药的脑浓度有影响，但我们的结果并不支持 C3435T 多态性参与自然临床条件下抗抑郁药的治疗反应和安全性的假设，证实了先前的疗效研究结果。尽管如此，一些方法上的局限性可能可以解释我们的负面结果。
Introduction: Pharmacogenetic factors may explain some of the interindividual variability of response to antidepressants in depressed patients. We focused on P-glycoprotein (P-GP), whose expression depends on a functional polymorphism of the ABCB1 gene (C3435T variants: dbSNP: rs1045642), the 3435CC genotype being linked to a high level of P-GP expression. Acting as an efflux pump at the blood-brain barrier, P-GP reduces the intracellular penetration of many drugs. Little is known about the interaction between P-GP and response to antidepressants. The objective of this study is to assess whether the response to antidepressants in depression differs in patients with the 3435CC genotype as compared to patients with the 3435CT and 3435TT genotypes. Methods: 117 in-patients with a major depressive episode requiring a new antidepressant treatment were enrolled in this prospective naturalistic 4-week study. Response to antidepressants was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, the Clinician Global Impression Improvement and Therapeutic Index, and weight change. ABCB1 genotyping was performed using the Taqman method. Clinical assessment was performed blind from genotypes. Results: We failed to show any significant effect of the ABCB1 polymorphism in position 3435 on antidepressant efficacy or tolerance. Discussion: While some in vitro studies showed an influence of P-GP on cerebral concentrations of antidepressants, our results do not support the hypothesis that the C3435T polymorphism is involved in therapeutic response and safety of antidepressants in naturalistic clinical conditions, confirming results of previous studies on efficacy. Nonetheless, some methodological limitations may explain our negative results.