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Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males

BACKGROUND: Previous research reported that individual differences in the stress response were moderated by an interaction between individuals’ life stress experience and the serotonin transporter-linked polymorphic region (5-HTTLPR), a common polymorphism located in the promoter region of the serot...

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Autores principales: Duman, Elif A, Canli, Turhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438516/
https://www.ncbi.nlm.nih.gov/pubmed/25995833
http://dx.doi.org/10.1186/s13587-015-0017-x
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author Duman, Elif A
Canli, Turhan
author_facet Duman, Elif A
Canli, Turhan
author_sort Duman, Elif A
collection PubMed
description BACKGROUND: Previous research reported that individual differences in the stress response were moderated by an interaction between individuals’ life stress experience and the serotonin transporter-linked polymorphic region (5-HTTLPR), a common polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4). Furthermore, this work suggested that individual differences in SLC6A4 DNA methylation could be one underlying mechanism by which stressful life events might regulate gene expression. The aim of this study was to understand the relation between early and recent life stress experiences, 5-HTTLPR genotype, and SLC6A4 methylation. In addition, we aimed to address how these factors influence gene expression and cortisol response to an acute psychosocial stressor, operationalized as the Trier Social Stress Test (TSST). In a sample of 105 Caucasian males, we collected early and recent life stress measures and blood samples to determine 5-HTTLPR genotype and SLC6A4 methylation. Furthermore, 71 of these participants provided blood and saliva samples before and after the TSST to measure changes in SLC6A4 and NR3C1 gene expression and cortisol response. RESULTS: Compared to S-group individuals, LL individuals responded with increased SLC6A4 mRNA levels to the TSST (t(66) = 3.71, P < .001) and also showed increased global methylation as a function of ELS (r (32) = .45, P = .008) and chronic stress (r (32) = .44, P = .010). Compared to LL individuals, S-group individuals showed reduced SLC6A4 mRNA levels (r (41) = −.31, P = .042) and increased F3 methylation (r (67) = .30, P = .015) as a function of ELS; as well as increased F1 methylation as a function of chronic stress and recent depressive symptoms (r = .41, P < .01), which correlated positively with NR3C1 expression (r (42) = .31, P = .040). CONCLUSIONS: Both early and recent life stress alter DNA methylation as a function of 5-HTTLPR genotype. Some of these changes are also reflected in gene expression and cortisol response, differentially affecting individuals’ stress response in a manner that may confer susceptibility or resilience for psychopathology upon experiencing stressful life events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13587-015-0017-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-44385162015-05-21 Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males Duman, Elif A Canli, Turhan Biol Mood Anxiety Disord Research BACKGROUND: Previous research reported that individual differences in the stress response were moderated by an interaction between individuals’ life stress experience and the serotonin transporter-linked polymorphic region (5-HTTLPR), a common polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4). Furthermore, this work suggested that individual differences in SLC6A4 DNA methylation could be one underlying mechanism by which stressful life events might regulate gene expression. The aim of this study was to understand the relation between early and recent life stress experiences, 5-HTTLPR genotype, and SLC6A4 methylation. In addition, we aimed to address how these factors influence gene expression and cortisol response to an acute psychosocial stressor, operationalized as the Trier Social Stress Test (TSST). In a sample of 105 Caucasian males, we collected early and recent life stress measures and blood samples to determine 5-HTTLPR genotype and SLC6A4 methylation. Furthermore, 71 of these participants provided blood and saliva samples before and after the TSST to measure changes in SLC6A4 and NR3C1 gene expression and cortisol response. RESULTS: Compared to S-group individuals, LL individuals responded with increased SLC6A4 mRNA levels to the TSST (t(66) = 3.71, P < .001) and also showed increased global methylation as a function of ELS (r (32) = .45, P = .008) and chronic stress (r (32) = .44, P = .010). Compared to LL individuals, S-group individuals showed reduced SLC6A4 mRNA levels (r (41) = −.31, P = .042) and increased F3 methylation (r (67) = .30, P = .015) as a function of ELS; as well as increased F1 methylation as a function of chronic stress and recent depressive symptoms (r = .41, P < .01), which correlated positively with NR3C1 expression (r (42) = .31, P = .040). CONCLUSIONS: Both early and recent life stress alter DNA methylation as a function of 5-HTTLPR genotype. Some of these changes are also reflected in gene expression and cortisol response, differentially affecting individuals’ stress response in a manner that may confer susceptibility or resilience for psychopathology upon experiencing stressful life events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13587-015-0017-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-14 /pmc/articles/PMC4438516/ /pubmed/25995833 http://dx.doi.org/10.1186/s13587-015-0017-x Text en © Duman and Canli; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Duman, Elif A
Canli, Turhan
Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title_full Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title_fullStr Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title_full_unstemmed Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title_short Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
title_sort influence of life stress, 5-httlpr genotype, and slc6a4 methylation on gene expression and stress response in healthy caucasian males
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438516/
https://www.ncbi.nlm.nih.gov/pubmed/25995833
http://dx.doi.org/10.1186/s13587-015-0017-x
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