ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study
Objective To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis. Background The DNA methylation profiling of periphe...
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| Veröffentlicht in: | Journal of periodontal research 2021-08, Vol.56 (4), p.710-725 |
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| creator | Hernández, Hernán G. Hernández‐Castañeda, Anne A. Pieschacón, Maria P. Arboleda, Humberto |
| description | Objective
To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis.
Background
The DNA methylation profiling of peripheral leukocytes as immune‐related tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.
Methods
A DNA methylation epigenome‐wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age‐matched and sex‐matched periodontally healthy controls. A trained periodontist performed the clinical evaluation. Global DNA methylation was estimated using methylation‐sensitive high‐resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.
Results
DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune‐related ontologies such as “detection of bacterium” and “antigen processing and presentation.”
Conclusion
The results of this study propose three new periodontitis‐related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes’ DNA methylome for biological interpretation of systemic immune‐related epigenetic patterns in periodontitis. |
| doi_str_mv | 10.1111/jre.12868 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_webof</sourceid><recordid>TN_cdi_webofscience_primary_000625187400001CitationCount</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2549537113</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3538-dee617982531565192e579d579e8ae408bec30028112bf59363dd86dcf33e0df3</originalsourceid><addsrcrecordid>eNqNkdFqFDEUhoModq1e-AIS8Eax2yaTSSbTu2XdtUppRRSkN0N2csbNkpmMSYZl7nwE7307n8S0u64gCAZCTpLvP_zJj9BTSk5pGmcbD6c0k0LeQxMqCJmSQvD7aEJIlk1ZLvMj9CiEDUl7UZQP0RFjQhApygn6cXO1LKg8wRfXn2f5CVadxjfL97zAygPWpmnAQxeNsnbELcT1aFUEjU2He_DGaZcuowm3B7Vre-VNcB3emrj-AyiL16BsXJ_jRW--QOda-Pnt-9ZowK-vZoe-Jil7Y13EIQ56fIweNMoGeLJfj9Gn5eLj_GJ6ef3m7Xx2Oa0ZZ3KqAQQtSplxRrngtMyAF6VOE6SCnMgV1Cw9XVKarRpeMsG0lkLXDWNAdMOO0Ytd3967rwOEWLUm1GCt6sANocrysqCE0Fwm9Plf6MYNvkvuqoznJWcFpSxRL3dU7V0IHpqq96ZVfqwoqW4Tq1Ji1V1iiX227zisWtAH8ndECZA7YAsr14TaQFfDAUuZioxTWeSpInRu4t03zt3QxSR99f_SRJ_taWNh_Lfl6t2Hxc77L8kNwQU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2549537113</pqid></control><display><type>article</type><title>ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study</title><source>Access via Wiley Online Library</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Hernández, Hernán G. ; Hernández‐Castañeda, Anne A. ; Pieschacón, Maria P. ; Arboleda, Humberto</creator><creatorcontrib>Hernández, Hernán G. ; Hernández‐Castañeda, Anne A. ; Pieschacón, Maria P. ; Arboleda, Humberto</creatorcontrib><description>Objective
To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis.
Background
The DNA methylation profiling of peripheral leukocytes as immune‐related tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.
Methods
A DNA methylation epigenome‐wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age‐matched and sex‐matched periodontally healthy controls. A trained periodontist performed the clinical evaluation. Global DNA methylation was estimated using methylation‐sensitive high‐resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.
Results
DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune‐related ontologies such as “detection of bacterium” and “antigen processing and presentation.”
Conclusion
The results of this study propose three new periodontitis‐related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes’ DNA methylome for biological interpretation of systemic immune‐related epigenetic patterns in periodontitis.</description><identifier>ISSN: 0022-3484</identifier><identifier>EISSN: 1600-0765</identifier><identifier>DOI: 10.1111/jre.12868</identifier><identifier>PMID: 33660869</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Antigen presentation ; Antigen processing ; Cytometry ; Dentistry ; Dentistry, Oral Surgery & Medicine ; Deoxyribonucleic acid ; DNA ; DNA fingerprinting ; DNA methylation ; Epigenetics ; epigenomics ; Gum disease ; Homeobox ; inflammation ; Leukocytes ; Life Sciences & Biomedicine ; Patients ; Periodontitis ; Science & Technology ; Zinc finger proteins</subject><ispartof>Journal of periodontal research, 2021-08, Vol.56 (4), p.710-725</ispartof><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2021 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>7</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000625187400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c3538-dee617982531565192e579d579e8ae408bec30028112bf59363dd86dcf33e0df3</citedby><cites>FETCH-LOGICAL-c3538-dee617982531565192e579d579e8ae408bec30028112bf59363dd86dcf33e0df3</cites><orcidid>0000-0001-8479-6269</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjre.12868$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjre.12868$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,39263,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33660869$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hernández, Hernán G.</creatorcontrib><creatorcontrib>Hernández‐Castañeda, Anne A.</creatorcontrib><creatorcontrib>Pieschacón, Maria P.</creatorcontrib><creatorcontrib>Arboleda, Humberto</creatorcontrib><title>ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study</title><title>Journal of periodontal research</title><addtitle>J PERIODONTAL RES</addtitle><addtitle>J Periodontal Res</addtitle><description>Objective
To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis.
Background
The DNA methylation profiling of peripheral leukocytes as immune‐related tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.
Methods
A DNA methylation epigenome‐wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age‐matched and sex‐matched periodontally healthy controls. A trained periodontist performed the clinical evaluation. Global DNA methylation was estimated using methylation‐sensitive high‐resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.
Results
DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune‐related ontologies such as “detection of bacterium” and “antigen processing and presentation.”
Conclusion
The results of this study propose three new periodontitis‐related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes’ DNA methylome for biological interpretation of systemic immune‐related epigenetic patterns in periodontitis.</description><subject>Antigen presentation</subject><subject>Antigen processing</subject><subject>Cytometry</subject><subject>Dentistry</subject><subject>Dentistry, Oral Surgery & Medicine</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fingerprinting</subject><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>epigenomics</subject><subject>Gum disease</subject><subject>Homeobox</subject><subject>inflammation</subject><subject>Leukocytes</subject><subject>Life Sciences & Biomedicine</subject><subject>Patients</subject><subject>Periodontitis</subject><subject>Science & Technology</subject><subject>Zinc finger proteins</subject><issn>0022-3484</issn><issn>1600-0765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><recordid>eNqNkdFqFDEUhoModq1e-AIS8Eax2yaTSSbTu2XdtUppRRSkN0N2csbNkpmMSYZl7nwE7307n8S0u64gCAZCTpLvP_zJj9BTSk5pGmcbD6c0k0LeQxMqCJmSQvD7aEJIlk1ZLvMj9CiEDUl7UZQP0RFjQhApygn6cXO1LKg8wRfXn2f5CVadxjfL97zAygPWpmnAQxeNsnbELcT1aFUEjU2He_DGaZcuowm3B7Vre-VNcB3emrj-AyiL16BsXJ_jRW--QOda-Pnt-9ZowK-vZoe-Jil7Y13EIQ56fIweNMoGeLJfj9Gn5eLj_GJ6ef3m7Xx2Oa0ZZ3KqAQQtSplxRrngtMyAF6VOE6SCnMgV1Cw9XVKarRpeMsG0lkLXDWNAdMOO0Ytd3967rwOEWLUm1GCt6sANocrysqCE0Fwm9Plf6MYNvkvuqoznJWcFpSxRL3dU7V0IHpqq96ZVfqwoqW4Tq1Ji1V1iiX227zisWtAH8ndECZA7YAsr14TaQFfDAUuZioxTWeSpInRu4t03zt3QxSR99f_SRJ_taWNh_Lfl6t2Hxc77L8kNwQU</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Hernández, Hernán G.</creator><creator>Hernández‐Castañeda, Anne A.</creator><creator>Pieschacón, Maria P.</creator><creator>Arboleda, Humberto</creator><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8479-6269</orcidid></search><sort><creationdate>202108</creationdate><title>ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study</title><author>Hernández, Hernán G. ; Hernández‐Castañeda, Anne A. ; Pieschacón, Maria P. ; Arboleda, Humberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-dee617982531565192e579d579e8ae408bec30028112bf59363dd86dcf33e0df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antigen presentation</topic><topic>Antigen processing</topic><topic>Cytometry</topic><topic>Dentistry</topic><topic>Dentistry, Oral Surgery & Medicine</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA fingerprinting</topic><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>epigenomics</topic><topic>Gum disease</topic><topic>Homeobox</topic><topic>inflammation</topic><topic>Leukocytes</topic><topic>Life Sciences & Biomedicine</topic><topic>Patients</topic><topic>Periodontitis</topic><topic>Science & Technology</topic><topic>Zinc finger proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hernández, Hernán G.</creatorcontrib><creatorcontrib>Hernández‐Castañeda, Anne A.</creatorcontrib><creatorcontrib>Pieschacón, Maria P.</creatorcontrib><creatorcontrib>Arboleda, Humberto</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of periodontal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hernández, Hernán G.</au><au>Hernández‐Castañeda, Anne A.</au><au>Pieschacón, Maria P.</au><au>Arboleda, Humberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study</atitle><jtitle>Journal of periodontal research</jtitle><stitle>J PERIODONTAL RES</stitle><addtitle>J Periodontal Res</addtitle><date>2021-08</date><risdate>2021</risdate><volume>56</volume><issue>4</issue><spage>710</spage><epage>725</epage><pages>710-725</pages><issn>0022-3484</issn><eissn>1600-0765</eissn><abstract>Objective
To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis.
Background
The DNA methylation profiling of peripheral leukocytes as immune‐related tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.
Methods
A DNA methylation epigenome‐wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age‐matched and sex‐matched periodontally healthy controls. A trained periodontist performed the clinical evaluation. Global DNA methylation was estimated using methylation‐sensitive high‐resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.
Results
DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune‐related ontologies such as “detection of bacterium” and “antigen processing and presentation.”
Conclusion
The results of this study propose three new periodontitis‐related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes’ DNA methylome for biological interpretation of systemic immune‐related epigenetic patterns in periodontitis.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>33660869</pmid><doi>10.1111/jre.12868</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8479-6269</orcidid></addata></record> |
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| ispartof | Journal of periodontal research, 2021-08, Vol.56 (4), p.710-725 |
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| subjects | Antigen presentation Antigen processing Cytometry Dentistry Dentistry, Oral Surgery & Medicine Deoxyribonucleic acid DNA DNA fingerprinting DNA methylation Epigenetics epigenomics Gum disease Homeobox inflammation Leukocytes Life Sciences & Biomedicine Patients Periodontitis Science & Technology Zinc finger proteins |
| title | ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study |
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