DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment
Abstract Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3+...
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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06847-z |
| _version_ | 1819042879137382400 |
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| author | Christof Brückmann Sumaiya A. Islam Julia L. MacIsaac Alexander M. Morin Kathrin N. Karle Adriana Di Santo Richard Wüst Immanuel Lang Anil Batra Michael S. Kobor Vanessa Nieratschker |
| author_facet | Christof Brückmann Sumaiya A. Islam Julia L. MacIsaac Alexander M. Morin Kathrin N. Karle Adriana Di Santo Richard Wüst Immanuel Lang Anil Batra Michael S. Kobor Vanessa Nieratschker |
| author_sort | Christof Brückmann |
| collection | DOAJ |
| description | Abstract Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3+ T-cells from pre- and post-treatment alcohol dependent patients, as well as closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment with healthy controls and were able to confirm 8 of those sites in additional analyses for differentially methylated regions. Comparing patients before and after a 3-week alcohol treatment program we revealed another unique set of 48 differentially methylated CpG sites. Additionally, we found that the mean global DNAm was significantly lower in patients prior to treatment compared to controls, but reverted back to levels similar to controls after treatment. We validated top-ranked hits derived from the epigenome-wide analysis by pyrosequencing and further replicated two of them in an independent cohort and confirmed differential DNAm of HECW2 and SRPK3 in whole blood. This study is the first to show widespread DNAm variation in a disease-relevant blood cell type and implicates HECW2 and SRPK3 DNAm as promising blood-based candidates to follow up in future studies. |
| first_indexed | 2024-12-21T09:47:54Z |
| format | Article |
| id | doaj.art-67c91b58713c4442abfb21d86e71c3f8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T09:47:54Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-67c91b58713c4442abfb21d86e71c3f82022-12-21T19:08:17ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-06847-zDNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatmentChristof Brückmann0Sumaiya A. Islam1Julia L. MacIsaac2Alexander M. Morin3Kathrin N. Karle4Adriana Di Santo5Richard Wüst6Immanuel Lang7Anil Batra8Michael S. Kobor9Vanessa Nieratschker10Department of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics, BC Children’s HospitalCentre for Molecular Medicine and Therapeutics, BC Children’s HospitalDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenDepartment of Medical Genetics, University of British ColumbiaDepartment of Psychiatry and Psychotherapy, University Hospital of TuebingenAbstract Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3+ T-cells from pre- and post-treatment alcohol dependent patients, as well as closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment with healthy controls and were able to confirm 8 of those sites in additional analyses for differentially methylated regions. Comparing patients before and after a 3-week alcohol treatment program we revealed another unique set of 48 differentially methylated CpG sites. Additionally, we found that the mean global DNAm was significantly lower in patients prior to treatment compared to controls, but reverted back to levels similar to controls after treatment. We validated top-ranked hits derived from the epigenome-wide analysis by pyrosequencing and further replicated two of them in an independent cohort and confirmed differential DNAm of HECW2 and SRPK3 in whole blood. This study is the first to show widespread DNAm variation in a disease-relevant blood cell type and implicates HECW2 and SRPK3 DNAm as promising blood-based candidates to follow up in future studies.https://doi.org/10.1038/s41598-017-06847-z |
| spellingShingle | Christof Brückmann Sumaiya A. Islam Julia L. MacIsaac Alexander M. Morin Kathrin N. Karle Adriana Di Santo Richard Wüst Immanuel Lang Anil Batra Michael S. Kobor Vanessa Nieratschker DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment Scientific Reports |
| title | DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment |
| title_full | DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment |
| title_fullStr | DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment |
| title_full_unstemmed | DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment |
| title_short | DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment |
| title_sort | dna methylation signatures of chronic alcohol dependence in purified cd3 t cells of patients undergoing alcohol treatment |
| url | https://doi.org/10.1038/s41598-017-06847-z |
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