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Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder
Major depressive disorder (MDD) is a serious mental disease with negative effects on both mental and physical health of the patient. Currently, antidepressants are among the major ways to ease or treat MDD. However, the existing antidepressants have limited efficacy in treating MDD, with a large fra...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093583/ https://www.ncbi.nlm.nih.gov/pubmed/32256400 http://dx.doi.org/10.3389/fpsyt.2020.00151 |
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author | Xin, Juncai Yuan, Meng Peng, Yonglin Wang, Ju |
author_facet | Xin, Juncai Yuan, Meng Peng, Yonglin Wang, Ju |
author_sort | Xin, Juncai |
collection | PubMed |
description | Major depressive disorder (MDD) is a serious mental disease with negative effects on both mental and physical health of the patient. Currently, antidepressants are among the major ways to ease or treat MDD. However, the existing antidepressants have limited efficacy in treating MDD, with a large fraction of patients either responding inadequately or differently to antidepressants during the treatment. Pharmacogenetics studies have found that the genetic features of some genes are associated with the antidepressant efficacy. In order to obtain a better understanding on the relationship between the genetic factors and antidepressant treatment response, we compiled a list of 233 single-nucleotide polymorphisms (SNPs) significantly associated with the antidepressant efficacy in treating MDD. Of the 13 non-synonymous SNPs in the list, three (rs1065852, rs3810651, and rs117986340) may influence the structures and function of the corresponding proteins. Besides, the influence of rs1065852 on the structure of CYP2D6 was further investigated via molecular dynamics simulations. Our results showed that compared to the native CYP2D6 the flexibility of the F-G loop was reduced in the mutant. As a portion of the substrate access channel, the lower flexibility of F-G loop may reduce the ability of the substrates to enter the channel, which may be the reason for the lower enzyme activity of mutant. This study may help us to understand the impact of genetic variation on antidepressant efficacy and provide clues for developing new antidepressants. |
format | Online Article Text |
id | pubmed-7093583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70935832020-04-01 Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder Xin, Juncai Yuan, Meng Peng, Yonglin Wang, Ju Front Psychiatry Psychiatry Major depressive disorder (MDD) is a serious mental disease with negative effects on both mental and physical health of the patient. Currently, antidepressants are among the major ways to ease or treat MDD. However, the existing antidepressants have limited efficacy in treating MDD, with a large fraction of patients either responding inadequately or differently to antidepressants during the treatment. Pharmacogenetics studies have found that the genetic features of some genes are associated with the antidepressant efficacy. In order to obtain a better understanding on the relationship between the genetic factors and antidepressant treatment response, we compiled a list of 233 single-nucleotide polymorphisms (SNPs) significantly associated with the antidepressant efficacy in treating MDD. Of the 13 non-synonymous SNPs in the list, three (rs1065852, rs3810651, and rs117986340) may influence the structures and function of the corresponding proteins. Besides, the influence of rs1065852 on the structure of CYP2D6 was further investigated via molecular dynamics simulations. Our results showed that compared to the native CYP2D6 the flexibility of the F-G loop was reduced in the mutant. As a portion of the substrate access channel, the lower flexibility of F-G loop may reduce the ability of the substrates to enter the channel, which may be the reason for the lower enzyme activity of mutant. This study may help us to understand the impact of genetic variation on antidepressant efficacy and provide clues for developing new antidepressants. Frontiers Media S.A. 2020-03-18 /pmc/articles/PMC7093583/ /pubmed/32256400 http://dx.doi.org/10.3389/fpsyt.2020.00151 Text en Copyright © 2020 Xin, Yuan, Peng and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Xin, Juncai Yuan, Meng Peng, Yonglin Wang, Ju Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title | Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title_full | Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title_fullStr | Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title_full_unstemmed | Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title_short | Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder |
title_sort | analysis of the deleterious single-nucleotide polymorphisms associated with antidepressant efficacy in major depressive disorder |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093583/ https://www.ncbi.nlm.nih.gov/pubmed/32256400 http://dx.doi.org/10.3389/fpsyt.2020.00151 |
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