Genetic variants in FKBP5 affecting response to antidepressant drug treatment
Genetic variants in FKBP5 affecting response to antidepressant drug treatment
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DOI：
10.2217/14622416.9.7.841
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发表时间：
2008-07-01
期刊：
影响因子：
2.1
通讯作者：
Brockmdller, Juergen
中科院分区：
文献类型：
--
作者：
Kirchheiner, Julia;Lorrh, Rainer;Brockmdller, Juergen
简介：下丘脑-垂体-肾上腺 (HPA) 轴的过度活跃是抑郁症的致病机制，HPA 轴基因的遗传多态性已被描述为影响抗抑郁药物的反应。特别是，FKBP5（糖皮质激素受体的辅助伴侣）的两个多态性与治疗反应密切相关。我们的目的是分析这些发现是否可以在其他具有可比性的重度抑郁症住院患者的不同样本中重现。方法：使用 PCR 限制性片段长度多态性和 Taqman(R) 实时 PCR 对 179 名住院患者进行了 FKBP5 基因内两个变异的基因分型，这些患者在抗抑郁药物治疗的前 3 周进行了监测。抗抑郁药物的早期反应以 3 周后汉密尔顿抑郁评分下降的百分比来评估，有反应者与无反应者的区别在于下降了 50%。结果：FKBP5 变体 rs3800373 和 rs1360780 高度相关，FKBP5 变体携带者有更高的反应机会的趋势（p = 0.04；比值比：1.8；95% CI：0.98-3.3）。在分析药物特异性亚组时，效果主要出现在接受抗抑郁药物组合或文拉法辛治疗的患者亚组中。结论：在这项研究中，FKBP5 变异对抗抑郁药物反应的影响在独立的抑郁症患者队列中得到了证实；然而，优势比为 1.8 时，效应大小比之前描述的要小。
Introduction: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression. Methods: Genotyping for the two variants within the FKBP5 gene was performed using PCR-restriction fragment length polymorphism and Taqman(R) real-time PCR in a cohort of 179 inpatients who were monitored for the first 3 weeks of antidepressant drug treatment. The early response to antidepressant drugs was assessed as percentage of decline in Hamilton depression score after 3 weeks, responders versus nonresponders were distinguished by a 50% decrease. Results: The FKBP5 variants rs3800373 and rs1360780 were highly linked, and carriers of the FKBP5 variants had a trend towards a higher chance to respond (p = 0.04; odds ratio: 1.8; 95% CI: 0.98-3.3). When analyzing drug-specific subgroups, the effect was seen mainly in the subgroups of patients treated with antidepressant drug combinations or with venlafaxine. Conclusion: In this study, an effect of FKBP5 variants on antidepressant drug response was confirmed in an independent cohort of depressed patients; however, with an odds ratio of 1.8 the effect size was smaller than that described earlier.