Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort
Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments. Using...
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creator | Alasaari, Jukka S Lagus, Markus Ollila, Hanna M Toivola, Auli Kivimäki, Mika Vahtera, Jussi Kronholm, Erkki Härmä, Mikko Puttonen, Sampsa Paunio, Tiina |
description | Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments.
Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.
We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p |
doi_str_mv | 10.1371/journal.pone.0045813 |
format | Article |
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Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.
We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01). There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58). In unadjusted (bivariate) analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively) to methylation levels.
Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional capability and experience of depressed mood in long-term stress.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0045813</identifier><identifier>PMID: 23029256</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Base Sequence ; Biology ; Bisulfite ; Bivariate analysis ; Burn out (Psychology) ; Burnout ; Burnout, Professional - genetics ; Care and treatment ; Chronic illnesses ; CpG Islands ; Deoxyribonucleic acid ; Depression - genetics ; Depression, Mental ; DNA ; DNA Methylation ; DNA sequencing ; Dopamine ; Ecological risk assessment ; Environmental effects ; Environmental stress ; Epidemiology ; Epigenetics ; Female ; Gene expression ; Gene polymorphism ; Gene sequencing ; Genomes ; Genomics ; Genotype ; Genotypes ; Health aspects ; Humans ; Leukocytes ; Medical personnel ; Medicine ; Mental depression ; Methylation ; Molecular Sequence Data ; Mood ; Nurses ; Occupational Diseases - genetics ; Occupational health ; Peripheral blood ; Polymorphism ; Polymorphism, Genetic ; Post traumatic stress disorder ; Practice ; Promoter Regions, Genetic ; Psychiatry ; Public health ; Residues ; Risk factors ; Sequence Analysis, DNA ; Serotonin ; Serotonin Plasma Membrane Transport Proteins - genetics ; Serotonin transporter ; Stress ; Stresses ; Studies ; Transcription ; Work Schedule Tolerance ; Working conditions ; Young Adult</subject><ispartof>PloS one, 2012-09, Vol.7 (9), p.e45813</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Alasaari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Alasaari et al 2012 Alasaari et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-beec13980c99d1f5eb569ad2a6af330ddc17087ffcd5dbd2cc809ec85660766f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461019/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461019/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23029256$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chiariotti, Lorenzo</contributor><creatorcontrib>Alasaari, Jukka S</creatorcontrib><creatorcontrib>Lagus, Markus</creatorcontrib><creatorcontrib>Ollila, Hanna M</creatorcontrib><creatorcontrib>Toivola, Auli</creatorcontrib><creatorcontrib>Kivimäki, Mika</creatorcontrib><creatorcontrib>Vahtera, Jussi</creatorcontrib><creatorcontrib>Kronholm, Erkki</creatorcontrib><creatorcontrib>Härmä, Mikko</creatorcontrib><creatorcontrib>Puttonen, Sampsa</creatorcontrib><creatorcontrib>Paunio, Tiina</creatorcontrib><title>Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments.
Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.
We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01). There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58). In unadjusted (bivariate) analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively) to methylation levels.
Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional capability and experience of depressed mood in long-term stress.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Bisulfite</subject><subject>Bivariate analysis</subject><subject>Burn out (Psychology)</subject><subject>Burnout</subject><subject>Burnout, Professional - genetics</subject><subject>Care and treatment</subject><subject>Chronic illnesses</subject><subject>CpG Islands</subject><subject>Deoxyribonucleic acid</subject><subject>Depression - genetics</subject><subject>Depression, Mental</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>DNA sequencing</subject><subject>Dopamine</subject><subject>Ecological risk assessment</subject><subject>Environmental effects</subject><subject>Environmental stress</subject><subject>Epidemiology</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Gene sequencing</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Medical personnel</subject><subject>Medicine</subject><subject>Mental depression</subject><subject>Methylation</subject><subject>Molecular Sequence Data</subject><subject>Mood</subject><subject>Nurses</subject><subject>Occupational Diseases - genetics</subject><subject>Occupational health</subject><subject>Peripheral blood</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Post traumatic stress disorder</subject><subject>Practice</subject><subject>Promoter Regions, Genetic</subject><subject>Psychiatry</subject><subject>Public health</subject><subject>Residues</subject><subject>Risk factors</subject><subject>Sequence Analysis, DNA</subject><subject>Serotonin</subject><subject>Serotonin Plasma Membrane Transport Proteins - genetics</subject><subject>Serotonin transporter</subject><subject>Stress</subject><subject>Stresses</subject><subject>Studies</subject><subject>Transcription</subject><subject>Work Schedule Tolerance</subject><subject>Working conditions</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQDguDDjEnTpM2LMIzrOrC44L_XkKZJm6VNapIurp_ejNNdpqAgeUi493dPLoeTZc8RXCNcorfXbvJW9OvRWbWGsCAVwg-yU8RwvqI5xA-P3ifZkxCuISS4ovRxdpJjmLOc0NPs17m9Md7ZQdkoehCiVyEAobWSMYD3nzZgULG77UU0zgKngQDb8QJ4Izsweje4qDzwqp27QXkXnTUWRC9sGJ3f91tlFUg1AezkgwLSdanxNHukRR_Us_k-y759OP-6_bi6vLrYbTeXK1mSKq5qpSTCrIKSsQZpompCmWhyQYXGGDaNRCWsSq1lQ5q6yaWsIFOyIpTCklKNz7KXB92xd4HPtgWOcE4JQbTCidgdiMaJaz56Mwh_y50w_E_B-ZYLH43sFZdlXdSCaS2wLjSrBYZEaJpLJitaapa03s2_TfWgGpl89aJfiC471nS8dTccFxRBtBd4NQt492NSIf5j5ZlqRdrKWO2SmBxMkHxTsCovigLTRK3_QqXTqMHIFBxtUn0x8GYxkJiofsZWTCHw3ZfP_89efV-yr4_YTok-dsH10z5VYQkWB1B6F4JX-t45BPk-93du8H3u-Zz7NPbi2PX7obug498tGQDA</recordid><startdate>20120928</startdate><enddate>20120928</enddate><creator>Alasaari, Jukka S</creator><creator>Lagus, Markus</creator><creator>Ollila, Hanna M</creator><creator>Toivola, Auli</creator><creator>Kivimäki, Mika</creator><creator>Vahtera, Jussi</creator><creator>Kronholm, Erkki</creator><creator>Härmä, Mikko</creator><creator>Puttonen, Sampsa</creator><creator>Paunio, Tiina</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120928</creationdate><title>Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort</title><author>Alasaari, Jukka S ; Lagus, Markus ; Ollila, Hanna M ; Toivola, Auli ; Kivimäki, Mika ; Vahtera, Jussi ; Kronholm, Erkki ; Härmä, Mikko ; Puttonen, Sampsa ; Paunio, Tiina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-beec13980c99d1f5eb569ad2a6af330ddc17087ffcd5dbd2cc809ec85660766f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Base Sequence</topic><topic>Biology</topic><topic>Bisulfite</topic><topic>Bivariate analysis</topic><topic>Burn out (Psychology)</topic><topic>Burnout</topic><topic>Burnout, Professional - genetics</topic><topic>Care and treatment</topic><topic>Chronic illnesses</topic><topic>CpG Islands</topic><topic>Deoxyribonucleic acid</topic><topic>Depression - genetics</topic><topic>Depression, Mental</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>DNA sequencing</topic><topic>Dopamine</topic><topic>Ecological risk assessment</topic><topic>Environmental effects</topic><topic>Environmental stress</topic><topic>Epidemiology</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Gene sequencing</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Medical personnel</topic><topic>Medicine</topic><topic>Mental depression</topic><topic>Methylation</topic><topic>Molecular Sequence Data</topic><topic>Mood</topic><topic>Nurses</topic><topic>Occupational Diseases - genetics</topic><topic>Occupational health</topic><topic>Peripheral blood</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Post traumatic stress disorder</topic><topic>Practice</topic><topic>Promoter Regions, Genetic</topic><topic>Psychiatry</topic><topic>Public health</topic><topic>Residues</topic><topic>Risk factors</topic><topic>Sequence Analysis, DNA</topic><topic>Serotonin</topic><topic>Serotonin Plasma Membrane Transport Proteins - 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We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments.
Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.
We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01). There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58). In unadjusted (bivariate) analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively) to methylation levels.
Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional capability and experience of depressed mood in long-term stress.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23029256</pmid><doi>10.1371/journal.pone.0045813</doi><tpages>e45813</tpages><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1326551683 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
subjects | Adolescent Adult Base Sequence Biology Bisulfite Bivariate analysis Burn out (Psychology) Burnout Burnout, Professional - genetics Care and treatment Chronic illnesses CpG Islands Deoxyribonucleic acid Depression - genetics Depression, Mental DNA DNA Methylation DNA sequencing Dopamine Ecological risk assessment Environmental effects Environmental stress Epidemiology Epigenetics Female Gene expression Gene polymorphism Gene sequencing Genomes Genomics Genotype Genotypes Health aspects Humans Leukocytes Medical personnel Medicine Mental depression Methylation Molecular Sequence Data Mood Nurses Occupational Diseases - genetics Occupational health Peripheral blood Polymorphism Polymorphism, Genetic Post traumatic stress disorder Practice Promoter Regions, Genetic Psychiatry Public health Residues Risk factors Sequence Analysis, DNA Serotonin Serotonin Plasma Membrane Transport Proteins - genetics Serotonin transporter Stress Stresses Studies Transcription Work Schedule Tolerance Working conditions Young Adult |
title | Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T19%3A18%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Environmental%20stress%20affects%20DNA%20methylation%20of%20a%20CpG%20rich%20promoter%20region%20of%20serotonin%20transporter%20gene%20in%20a%20nurse%20cohort&rft.jtitle=PloS%20one&rft.au=Alasaari,%20Jukka%20S&rft.date=2012-09-28&rft.volume=7&rft.issue=9&rft.spage=e45813&rft.pages=e45813-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0045813&rft_dat=%3Cgale_plos_%3EA498244436%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326551683&rft_id=info:pmid/23029256&rft_galeid=A498244436&rft_doaj_id=oai_doaj_org_article_c7b4ba9ffa3f4f9ba305af62c9c867f9&rfr_iscdi=true |