Mitjans Marina, Catalán Rosa, Vázquez Mireia, González-Rodríguez Alex, Penadés Rafael, Pons Alexandre, Massana Guillem, Munro Janet, Arranz Maria J, Arias Bárbara
aAnthropology Section, Department of Animal Biology, Faculty of Biology, University of Barcelona/Biomedicine Institute of the University of Barcelona (IBUB) bClinical Institute of Neuroscience, Hospital Clínic cDepartment of Psychiatry and Clinical Psychobiology, University of Barcelona dBiomedical Research Institute Agustí Pi i Sunyer (IDIBAPS) eTeaching and Research Foundation Mútua Terrassa, University Hospital Mútua Terrassa, Terrassa, Spain/Santa Creu i Sant Pau Hospital, Barcelona fCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain gOptimal Medicine Limited, London, UK.
Pharmacogenet Genomics. 2015 May;25(5):274-7. doi: 10.1097/FPC.0000000000000132.
Clozapine is an atypical antipsychotic drug known as being more effective compared with traditional antipsychotics for patients with poor response or resistance to treatment. It has been demonstrated that clozapine modulates hypothalamic-pituitary-adrenal activity and affects central brain-derived neurotrophic factor levels, which could explain part of its therapeutic efficacy. In this study, we investigated the role of genes related to the hypothalamic-pituitary-adrenal axis (FKBP5 and NR3C1) and neurotrophic factors (BDNF and NTRK2) in clinical response to clozapine in 591 schizophrenia patients. We found significant allelic and genotype associations between FKBP5-rs1360780, NTRK2-rs1778929 and NTRK2-rs10465180 polymorphisms and clozapine response. The haplotypes composed of rs1360780-rs3777747-rs17542466-rs2766533 (FKBP5) and rs1619120-rs1778929-rs10465180 (NTRK2) were also nominally significant. Our results suggest that genetic variability in FKBP5 and NTRK2 genes may partially explain clinical response to clozapine. Further studies are needed to clarify the involvement of these genes in clinical response to atypical antipsychotics.
氯氮平是一种非典型抗精神病药物，已知对于治疗反应不佳或有抗药性的患者，它比传统抗精神病药物更有效。已证明氯氮平可调节下丘脑 - 垂体 - 肾上腺活动，并影响中枢脑源性神经营养因子水平，这可能解释其部分治疗效果。在本研究中，我们调查了591例精神分裂症患者中与下丘脑 - 垂体 - 肾上腺轴相关的基因（FKBP5和NR3C1）以及神经营养因子（BDNF和NTRK2）在对氯氮平临床反应中的作用。我们发现FKBP5的rs1360780、NTRK2的rs1778929和NTRK2的rs10465180多态性与氯氮平反应之间存在显著的等位基因和基因型关联。由rs1360780 - rs3777747 - rs17542466 - rs2766533（FKBP5）和rs1619120 - rs1778929 - rs10465180（NTRK2）组成的单倍型也具有名义上的显著性。我们的结果表明，FKBP5和NTRK2基因的遗传变异性可能部分解释对氯氮平的临床反应。需要进一步研究以阐明这些基因在非典型抗精神病药物临床反应中的作用。
