ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis
Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulp...
Ausführliche Beschreibung
Autor*in: |
Teresa Infante [verfasserIn] Monica Franzese [verfasserIn] Antonio Ruocco [verfasserIn] Concetta Schiano [verfasserIn] Ornella Affinito [verfasserIn] Katia Pane [verfasserIn] Domenico Memoli [verfasserIn] Francesca Rizzo [verfasserIn] Alessandro Weisz [verfasserIn] Paola Bontempo [verfasserIn] Vincenzo Grimaldi [verfasserIn] Liberato Berrino [verfasserIn] Andrea Soricelli [verfasserIn] Ciro Mauro [verfasserIn] Claudio Napoli [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Übergeordnetes Werk: |
In: Epigenetics - Taylor & Francis Group, 2023, 17(2022), 5, Seite 547-563 |
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Übergeordnetes Werk: |
volume:17 ; year:2022 ; number:5 ; pages:547-563 |
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Link aufrufen |
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DOI / URN: |
10.1080/15592294.2021.1939481 |
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Katalog-ID: |
DOAJ098186663 |
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520 | |a Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. | ||
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10.1080/15592294.2021.1939481 doi (DE-627)DOAJ098186663 (DE-599)DOAJ91ad99c7794d4348aa5cd12448a31186 DE-627 ger DE-627 rakwb eng QH426-470 Teresa Infante verfasserin aut ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. acute coronary syndrome epigenetics dna methylation t lymphocytes Genetics Monica Franzese verfasserin aut Antonio Ruocco verfasserin aut Concetta Schiano verfasserin aut Ornella Affinito verfasserin aut Katia Pane verfasserin aut Domenico Memoli verfasserin aut Francesca Rizzo verfasserin aut Alessandro Weisz verfasserin aut Paola Bontempo verfasserin aut Vincenzo Grimaldi verfasserin aut Liberato Berrino verfasserin aut Andrea Soricelli verfasserin aut Ciro Mauro verfasserin aut Claudio Napoli verfasserin aut In Epigenetics Taylor & Francis Group, 2023 17(2022), 5, Seite 547-563 (DE-627)516805320 (DE-600)2248598-3 15592308 nnns volume:17 year:2022 number:5 pages:547-563 https://doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/article/91ad99c7794d4348aa5cd12448a31186 kostenfrei http://dx.doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/toc/1559-2294 Journal toc kostenfrei https://doaj.org/toc/1559-2308 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2026 GBV_ILN_2034 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2111 GBV_ILN_2129 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 17 2022 5 547-563 |
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10.1080/15592294.2021.1939481 doi (DE-627)DOAJ098186663 (DE-599)DOAJ91ad99c7794d4348aa5cd12448a31186 DE-627 ger DE-627 rakwb eng QH426-470 Teresa Infante verfasserin aut ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. acute coronary syndrome epigenetics dna methylation t lymphocytes Genetics Monica Franzese verfasserin aut Antonio Ruocco verfasserin aut Concetta Schiano verfasserin aut Ornella Affinito verfasserin aut Katia Pane verfasserin aut Domenico Memoli verfasserin aut Francesca Rizzo verfasserin aut Alessandro Weisz verfasserin aut Paola Bontempo verfasserin aut Vincenzo Grimaldi verfasserin aut Liberato Berrino verfasserin aut Andrea Soricelli verfasserin aut Ciro Mauro verfasserin aut Claudio Napoli verfasserin aut In Epigenetics Taylor & Francis Group, 2023 17(2022), 5, Seite 547-563 (DE-627)516805320 (DE-600)2248598-3 15592308 nnns volume:17 year:2022 number:5 pages:547-563 https://doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/article/91ad99c7794d4348aa5cd12448a31186 kostenfrei http://dx.doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/toc/1559-2294 Journal toc kostenfrei https://doaj.org/toc/1559-2308 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2026 GBV_ILN_2034 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2111 GBV_ILN_2129 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 17 2022 5 547-563 |
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10.1080/15592294.2021.1939481 doi (DE-627)DOAJ098186663 (DE-599)DOAJ91ad99c7794d4348aa5cd12448a31186 DE-627 ger DE-627 rakwb eng QH426-470 Teresa Infante verfasserin aut ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. acute coronary syndrome epigenetics dna methylation t lymphocytes Genetics Monica Franzese verfasserin aut Antonio Ruocco verfasserin aut Concetta Schiano verfasserin aut Ornella Affinito verfasserin aut Katia Pane verfasserin aut Domenico Memoli verfasserin aut Francesca Rizzo verfasserin aut Alessandro Weisz verfasserin aut Paola Bontempo verfasserin aut Vincenzo Grimaldi verfasserin aut Liberato Berrino verfasserin aut Andrea Soricelli verfasserin aut Ciro Mauro verfasserin aut Claudio Napoli verfasserin aut In Epigenetics Taylor & Francis Group, 2023 17(2022), 5, Seite 547-563 (DE-627)516805320 (DE-600)2248598-3 15592308 nnns volume:17 year:2022 number:5 pages:547-563 https://doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/article/91ad99c7794d4348aa5cd12448a31186 kostenfrei http://dx.doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/toc/1559-2294 Journal toc kostenfrei https://doaj.org/toc/1559-2308 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2026 GBV_ILN_2034 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2111 GBV_ILN_2129 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 17 2022 5 547-563 |
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10.1080/15592294.2021.1939481 doi (DE-627)DOAJ098186663 (DE-599)DOAJ91ad99c7794d4348aa5cd12448a31186 DE-627 ger DE-627 rakwb eng QH426-470 Teresa Infante verfasserin aut ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. acute coronary syndrome epigenetics dna methylation t lymphocytes Genetics Monica Franzese verfasserin aut Antonio Ruocco verfasserin aut Concetta Schiano verfasserin aut Ornella Affinito verfasserin aut Katia Pane verfasserin aut Domenico Memoli verfasserin aut Francesca Rizzo verfasserin aut Alessandro Weisz verfasserin aut Paola Bontempo verfasserin aut Vincenzo Grimaldi verfasserin aut Liberato Berrino verfasserin aut Andrea Soricelli verfasserin aut Ciro Mauro verfasserin aut Claudio Napoli verfasserin aut In Epigenetics Taylor & Francis Group, 2023 17(2022), 5, Seite 547-563 (DE-627)516805320 (DE-600)2248598-3 15592308 nnns volume:17 year:2022 number:5 pages:547-563 https://doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/article/91ad99c7794d4348aa5cd12448a31186 kostenfrei http://dx.doi.org/10.1080/15592294.2021.1939481 kostenfrei https://doaj.org/toc/1559-2294 Journal toc kostenfrei https://doaj.org/toc/1559-2308 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2026 GBV_ILN_2034 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2111 GBV_ILN_2129 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 17 2022 5 547-563 |
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Teresa Infante @@aut@@ Monica Franzese @@aut@@ Antonio Ruocco @@aut@@ Concetta Schiano @@aut@@ Ornella Affinito @@aut@@ Katia Pane @@aut@@ Domenico Memoli @@aut@@ Francesca Rizzo @@aut@@ Alessandro Weisz @@aut@@ Paola Bontempo @@aut@@ Vincenzo Grimaldi @@aut@@ Liberato Berrino @@aut@@ Andrea Soricelli @@aut@@ Ciro Mauro @@aut@@ Claudio Napoli @@aut@@ |
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Teresa Infante misc QH426-470 misc acute coronary syndrome misc epigenetics misc dna methylation misc t lymphocytes misc Genetics ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis |
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QH426-470 ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis acute coronary syndrome epigenetics dna methylation t lymphocytes |
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ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis |
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abca1, tcf7, nfatc1, prkcz, and pdgfa dna methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis |
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ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis |
abstract |
Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. |
abstractGer |
Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. |
abstract_unstemmed |
Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+ vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. |
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ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis |
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