Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation
The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine ( ) and the inhibitory receptor ( ) in naïve and memory CD8+ T cell...
Gespeichert in:
| Veröffentlicht in: | Clinical epigenetics 2016-11, Vol.8 (1), p.116-116, Article 116 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 116 |
|---|---|
| container_issue | 1 |
| container_start_page | 116 |
| container_title | Clinical epigenetics |
| container_volume | 8 |
| creator | Boer, Karin de Wit, L Elly A Peters, Fleur S Hesselink, Dennis A Hofland, Leo J Betjes, Michiel G H Looman, Caspar W N Baan, Carla C |
| description | The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine
(
) and the inhibitory receptor
(
) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included.
CpGs in the promoter regions of both
and
were significantly (
|
| doi_str_mv | 10.1186/s13148-016-0288-0 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5112717</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A470585297</galeid><sourcerecordid>A470585297</sourcerecordid><originalsourceid>FETCH-LOGICAL-c564t-e2eb0cd7b14e3b3bd4fd7404502ff932465103bb5b6146678828e607921a3edd3</originalsourceid><addsrcrecordid>eNptUk1v1DAUjBCIVqU_gAuyxIVLip_txM4FqSqfUgUX4Go58fOul8Re7CzSSvx4nN2yUER8iN94ZvyeNVX1FOgVgGpfZuAgVE2hrSlTZfOgOi-4qiVV_OFpL5uz6jLnDS0f77oO6OPqjEnVFZPuvPr51SRvZh9DJj6Q1x-vyYTzej8eMBJdQWdMDlOpVmaaDDHBkm2Kq1QqtMSimdcEFrUZxwV2M0m4weHgUCpM5Ju3AfdkTibk7WjCfLB_Uj1yZsx4efe_qL68ffP55n19--ndh5vr23poWjHXyLCng5U9COQ9761wVgoqGsqc6zgTbQOU933TtyDaVirFFLZUdgwMR2v5RfXq6Lvd9aXlAUNpZNTb5CeT9joar--fBL_Wq_hDNwBMgiwGL-4MUvy-wzzryecBxzIJxl3WoITgSxNdoT7_h7qJuxTKeAurBQaMwR_WyoyofXCx3DsspvpaSNqohnXLtVf_YZVlcfJDDOh8we8J4CgYUsw5oTvNCFQvqdHH1OiSGr2kRtOiefb345wUvzPCfwHyA710</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1846121221</pqid></control><display><type>article</type><title>Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>SpringerLink Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><creator>Boer, Karin ; de Wit, L Elly A ; Peters, Fleur S ; Hesselink, Dennis A ; Hofland, Leo J ; Betjes, Michiel G H ; Looman, Caspar W N ; Baan, Carla C</creator><creatorcontrib>Boer, Karin ; de Wit, L Elly A ; Peters, Fleur S ; Hesselink, Dennis A ; Hofland, Leo J ; Betjes, Michiel G H ; Looman, Caspar W N ; Baan, Carla C</creatorcontrib><description>The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine
(
) and the inhibitory receptor
(
) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included.
CpGs in the promoter regions of both
and
were significantly (
< 0.001) higher methylated in the naïve CD8+ T cells compared to the memory T cell subsets. The methylation status of both
and
inversely correlated with the percentage of IFNγ or PD1-producing cells. Before transplantation, the methylation status of both
and
was not significantly different from healthy donors. At 3 months after transplantation, irrespective of rejection and subsequent anti-rejection therapy, the
methylation was significantly higher in the differentiated effector memory CD45RA+ (EMRA) CD8+ T cells (
= 0.01) whereas the PD1 methylation was significantly higher in all memory CD8+ T cell subsets (CD27+ memory;
= 0.02: CD27- memory;
= 0.02: EMRA;
= 0.002). Comparing the increase in methylation in the first 3 months after transplantation between rejectors and non-rejectors demonstrated a significantly more prominent increase in the
methylation in the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase in non-rejectors 1.9%,
= 0.04). The increase in DNA methylation in the other memory CD8+ T cells was not significantly different between rejectors and non-rejectors. At 12 months after transplantation, the methylation of both
and
returned to baseline levels.
The DNA methylation of both
and
increases the first 3 months after transplantation in memory CD8+ T cells in kidney transplant recipients. This increase was irrespective of a rejection episode indicating that general factors of the kidney transplantation procedure, including the use of immunosuppressive medication, contribute to these variations in DNA methylation.</description><identifier>ISSN: 1868-7075</identifier><identifier>ISSN: 1868-7083</identifier><identifier>EISSN: 1868-7083</identifier><identifier>EISSN: 1868-7075</identifier><identifier>DOI: 10.1186/s13148-016-0288-0</identifier><identifier>PMID: 27891189</identifier><language>eng</language><publisher>Germany: BioMed Central Ltd</publisher><subject>Adult ; Aged ; CD8-Positive T-Lymphocytes - metabolism ; Complications and side effects ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene expression ; Genetic aspects ; Genetic variation ; Graft rejection ; Graft Rejection - blood ; Graft Rejection - genetics ; Health aspects ; Humans ; Interferon-gamma - genetics ; Interferon-gamma - metabolism ; Kidney Transplantation ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor - genetics ; Programmed Cell Death 1 Receptor - metabolism ; Risk factors</subject><ispartof>Clinical epigenetics, 2016-11, Vol.8 (1), p.116-116, Article 116</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-e2eb0cd7b14e3b3bd4fd7404502ff932465103bb5b6146678828e607921a3edd3</citedby><cites>FETCH-LOGICAL-c564t-e2eb0cd7b14e3b3bd4fd7404502ff932465103bb5b6146678828e607921a3edd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112717/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112717/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27891189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boer, Karin</creatorcontrib><creatorcontrib>de Wit, L Elly A</creatorcontrib><creatorcontrib>Peters, Fleur S</creatorcontrib><creatorcontrib>Hesselink, Dennis A</creatorcontrib><creatorcontrib>Hofland, Leo J</creatorcontrib><creatorcontrib>Betjes, Michiel G H</creatorcontrib><creatorcontrib>Looman, Caspar W N</creatorcontrib><creatorcontrib>Baan, Carla C</creatorcontrib><title>Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation</title><title>Clinical epigenetics</title><addtitle>Clin Epigenetics</addtitle><description>The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine
(
) and the inhibitory receptor
(
) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included.
CpGs in the promoter regions of both
and
were significantly (
< 0.001) higher methylated in the naïve CD8+ T cells compared to the memory T cell subsets. The methylation status of both
and
inversely correlated with the percentage of IFNγ or PD1-producing cells. Before transplantation, the methylation status of both
and
was not significantly different from healthy donors. At 3 months after transplantation, irrespective of rejection and subsequent anti-rejection therapy, the
methylation was significantly higher in the differentiated effector memory CD45RA+ (EMRA) CD8+ T cells (
= 0.01) whereas the PD1 methylation was significantly higher in all memory CD8+ T cell subsets (CD27+ memory;
= 0.02: CD27- memory;
= 0.02: EMRA;
= 0.002). Comparing the increase in methylation in the first 3 months after transplantation between rejectors and non-rejectors demonstrated a significantly more prominent increase in the
methylation in the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase in non-rejectors 1.9%,
= 0.04). The increase in DNA methylation in the other memory CD8+ T cells was not significantly different between rejectors and non-rejectors. At 12 months after transplantation, the methylation of both
and
returned to baseline levels.
The DNA methylation of both
and
increases the first 3 months after transplantation in memory CD8+ T cells in kidney transplant recipients. This increase was irrespective of a rejection episode indicating that general factors of the kidney transplantation procedure, including the use of immunosuppressive medication, contribute to these variations in DNA methylation.</description><subject>Adult</subject><subject>Aged</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Complications and side effects</subject><subject>CpG Islands</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic variation</subject><subject>Graft rejection</subject><subject>Graft Rejection - blood</subject><subject>Graft Rejection - genetics</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - metabolism</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Programmed Cell Death 1 Receptor - genetics</subject><subject>Programmed Cell Death 1 Receptor - metabolism</subject><subject>Risk factors</subject><issn>1868-7075</issn><issn>1868-7083</issn><issn>1868-7083</issn><issn>1868-7075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptUk1v1DAUjBCIVqU_gAuyxIVLip_txM4FqSqfUgUX4Go58fOul8Re7CzSSvx4nN2yUER8iN94ZvyeNVX1FOgVgGpfZuAgVE2hrSlTZfOgOi-4qiVV_OFpL5uz6jLnDS0f77oO6OPqjEnVFZPuvPr51SRvZh9DJj6Q1x-vyYTzej8eMBJdQWdMDlOpVmaaDDHBkm2Kq1QqtMSimdcEFrUZxwV2M0m4weHgUCpM5Ju3AfdkTibk7WjCfLB_Uj1yZsx4efe_qL68ffP55n19--ndh5vr23poWjHXyLCng5U9COQ9761wVgoqGsqc6zgTbQOU933TtyDaVirFFLZUdgwMR2v5RfXq6Lvd9aXlAUNpZNTb5CeT9joar--fBL_Wq_hDNwBMgiwGL-4MUvy-wzzryecBxzIJxl3WoITgSxNdoT7_h7qJuxTKeAurBQaMwR_WyoyofXCx3DsspvpaSNqohnXLtVf_YZVlcfJDDOh8we8J4CgYUsw5oTvNCFQvqdHH1OiSGr2kRtOiefb345wUvzPCfwHyA710</recordid><startdate>20161116</startdate><enddate>20161116</enddate><creator>Boer, Karin</creator><creator>de Wit, L Elly A</creator><creator>Peters, Fleur S</creator><creator>Hesselink, Dennis A</creator><creator>Hofland, Leo J</creator><creator>Betjes, Michiel G H</creator><creator>Looman, Caspar W N</creator><creator>Baan, Carla C</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161116</creationdate><title>Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation</title><author>Boer, Karin ; de Wit, L Elly A ; Peters, Fleur S ; Hesselink, Dennis A ; Hofland, Leo J ; Betjes, Michiel G H ; Looman, Caspar W N ; Baan, Carla C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-e2eb0cd7b14e3b3bd4fd7404502ff932465103bb5b6146678828e607921a3edd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Complications and side effects</topic><topic>CpG Islands</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetic variation</topic><topic>Graft rejection</topic><topic>Graft Rejection - blood</topic><topic>Graft Rejection - genetics</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - metabolism</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Programmed Cell Death 1 Receptor - genetics</topic><topic>Programmed Cell Death 1 Receptor - metabolism</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boer, Karin</creatorcontrib><creatorcontrib>de Wit, L Elly A</creatorcontrib><creatorcontrib>Peters, Fleur S</creatorcontrib><creatorcontrib>Hesselink, Dennis A</creatorcontrib><creatorcontrib>Hofland, Leo J</creatorcontrib><creatorcontrib>Betjes, Michiel G H</creatorcontrib><creatorcontrib>Looman, Caspar W N</creatorcontrib><creatorcontrib>Baan, Carla C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical epigenetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boer, Karin</au><au>de Wit, L Elly A</au><au>Peters, Fleur S</au><au>Hesselink, Dennis A</au><au>Hofland, Leo J</au><au>Betjes, Michiel G H</au><au>Looman, Caspar W N</au><au>Baan, Carla C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation</atitle><jtitle>Clinical epigenetics</jtitle><addtitle>Clin Epigenetics</addtitle><date>2016-11-16</date><risdate>2016</risdate><volume>8</volume><issue>1</issue><spage>116</spage><epage>116</epage><pages>116-116</pages><artnum>116</artnum><issn>1868-7075</issn><issn>1868-7083</issn><eissn>1868-7083</eissn><eissn>1868-7075</eissn><abstract>The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine
(
) and the inhibitory receptor
(
) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included.
CpGs in the promoter regions of both
and
were significantly (
< 0.001) higher methylated in the naïve CD8+ T cells compared to the memory T cell subsets. The methylation status of both
and
inversely correlated with the percentage of IFNγ or PD1-producing cells. Before transplantation, the methylation status of both
and
was not significantly different from healthy donors. At 3 months after transplantation, irrespective of rejection and subsequent anti-rejection therapy, the
methylation was significantly higher in the differentiated effector memory CD45RA+ (EMRA) CD8+ T cells (
= 0.01) whereas the PD1 methylation was significantly higher in all memory CD8+ T cell subsets (CD27+ memory;
= 0.02: CD27- memory;
= 0.02: EMRA;
= 0.002). Comparing the increase in methylation in the first 3 months after transplantation between rejectors and non-rejectors demonstrated a significantly more prominent increase in the
methylation in the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase in non-rejectors 1.9%,
= 0.04). The increase in DNA methylation in the other memory CD8+ T cells was not significantly different between rejectors and non-rejectors. At 12 months after transplantation, the methylation of both
and
returned to baseline levels.
The DNA methylation of both
and
increases the first 3 months after transplantation in memory CD8+ T cells in kidney transplant recipients. This increase was irrespective of a rejection episode indicating that general factors of the kidney transplantation procedure, including the use of immunosuppressive medication, contribute to these variations in DNA methylation.</abstract><cop>Germany</cop><pub>BioMed Central Ltd</pub><pmid>27891189</pmid><doi>10.1186/s13148-016-0288-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1868-7075 |
| ispartof | Clinical epigenetics, 2016-11, Vol.8 (1), p.116-116, Article 116 |
| issn | 1868-7075 1868-7083 1868-7083 1868-7075 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5112717 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Springer Nature OA Free Journals |
| subjects | Adult Aged CD8-Positive T-Lymphocytes - metabolism Complications and side effects CpG Islands DNA Methylation Epigenesis, Genetic Female Gene expression Genetic aspects Genetic variation Graft rejection Graft Rejection - blood Graft Rejection - genetics Health aspects Humans Interferon-gamma - genetics Interferon-gamma - metabolism Kidney Transplantation Male Middle Aged Programmed Cell Death 1 Receptor - genetics Programmed Cell Death 1 Receptor - metabolism Risk factors |
| title | Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T01%3A54%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Variations%20in%20DNA%20methylation%20of%20interferon%20gamma%20and%20programmed%20death%201%20in%20allograft%20rejection%20after%20kidney%20transplantation&rft.jtitle=Clinical%20epigenetics&rft.au=Boer,%20Karin&rft.date=2016-11-16&rft.volume=8&rft.issue=1&rft.spage=116&rft.epage=116&rft.pages=116-116&rft.artnum=116&rft.issn=1868-7075&rft.eissn=1868-7083&rft_id=info:doi/10.1186/s13148-016-0288-0&rft_dat=%3Cgale_pubme%3EA470585297%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1846121221&rft_id=info:pmid/27891189&rft_galeid=A470585297&rfr_iscdi=true |