Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine response: association with FKBP5 and NTRK2 genes

Pharmacogenetics and Genomics
Marina MitjansBárbara Arias

Abstract

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.

References

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Citations

Mar 31, 2017·International Journal of Molecular Sciences·Matea Nikolac PerkovicNela Pivac
Feb 9, 2016·European Psychiatry : the Journal of the Association of European Psychiatrists·S CargninS Terrazzino
Mar 13, 2018·Current Opinion in Psychiatry·Clement C ZaiJames L Kennedy
Jul 10, 2018·Current Opinion in Psychiatry·Kevin J LiLynn E DeLisi
Aug 25, 2016·European Archives of Psychiatry and Clinical Neuroscience·Marina MihaljevicNadja P Maric
Aug 11, 2018·Frontiers in Psychiatry·Ruta SamanaiteAlice Egerton
Dec 15, 2020·Behavioural Brain Research·Maria J ArranzMarta H Hernández

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Methods Mentioned

BETA
PCR

Software Mentioned

Plink
haplo
stat
R
Haploview
EpiInfo

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