Cargando…

Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients

It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant th...

Descripción completa

Detalles Bibliográficos
Autores principales: Kao, Chung-Feng, Liu, Yu-Li, Yu, Younger W.-Y., Yang, Albert C., Lin, Eugene, Kuo, Po-Hsiu, Tsai, Shih-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934385/
https://www.ncbi.nlm.nih.gov/pubmed/29725086
http://dx.doi.org/10.1038/s41598-018-25529-y
_version_ 1783320101846515712
author Kao, Chung-Feng
Liu, Yu-Li
Yu, Younger W.-Y.
Yang, Albert C.
Lin, Eugene
Kuo, Po-Hsiu
Tsai, Shih-Jen
author_facet Kao, Chung-Feng
Liu, Yu-Li
Yu, Younger W.-Y.
Yang, Albert C.
Lin, Eugene
Kuo, Po-Hsiu
Tsai, Shih-Jen
author_sort Kao, Chung-Feng
collection PubMed
description It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455). Measures of antidepressant therapeutic efficacy were evaluated using the 21-item Hamilton Rating Scale for Depression. Our single-marker and gene-based analyses with ten genes related to the neurotrophic pathway identified 6 polymorphisms that reached a significant level (p-value < 5.0 × 10(−3)) in both meta- and mega-analyses in antidepressant therapeutic response. One polymorphism was mapped to BDNF and 5 other polymorphisms were mapped to VEGFA. For case-control association study, we found that all of these reported polymorphisms and genes did not reach a suggestive level. The present study supported a role of BDNF and VEGFA variants in MDD therapeutic response.
format Online
Article
Text
id pubmed-5934385
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-59343852018-05-10 Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients Kao, Chung-Feng Liu, Yu-Li Yu, Younger W.-Y. Yang, Albert C. Lin, Eugene Kuo, Po-Hsiu Tsai, Shih-Jen Sci Rep Article It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455). Measures of antidepressant therapeutic efficacy were evaluated using the 21-item Hamilton Rating Scale for Depression. Our single-marker and gene-based analyses with ten genes related to the neurotrophic pathway identified 6 polymorphisms that reached a significant level (p-value < 5.0 × 10(−3)) in both meta- and mega-analyses in antidepressant therapeutic response. One polymorphism was mapped to BDNF and 5 other polymorphisms were mapped to VEGFA. For case-control association study, we found that all of these reported polymorphisms and genes did not reach a suggestive level. The present study supported a role of BDNF and VEGFA variants in MDD therapeutic response. Nature Publishing Group UK 2018-05-03 /pmc/articles/PMC5934385/ /pubmed/29725086 http://dx.doi.org/10.1038/s41598-018-25529-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kao, Chung-Feng
Liu, Yu-Li
Yu, Younger W.-Y.
Yang, Albert C.
Lin, Eugene
Kuo, Po-Hsiu
Tsai, Shih-Jen
Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title_full Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title_fullStr Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title_full_unstemmed Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title_short Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
title_sort gene-based analysis of genes related to neurotrophic pathway suggests association of bdnf and vegfa with antidepressant treatment-response in depressed patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934385/
https://www.ncbi.nlm.nih.gov/pubmed/29725086
http://dx.doi.org/10.1038/s41598-018-25529-y
work_keys_str_mv AT kaochungfeng genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT liuyuli genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT yuyoungerwy genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT yangalbertc genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT lineugene genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT kuopohsiu genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients
AT tsaishihjen genebasedanalysisofgenesrelatedtoneurotrophicpathwaysuggestsassociationofbdnfandvegfawithantidepressanttreatmentresponseindepressedpatients