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Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study

OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from...

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Autores principales: Svendsen, Anders J., Gervin, Kristina, Lyle, Robert, Christiansen, Lene, Kyvik, Kirsten, Junker, Peter, Nielsen, Christian, Houen, Gunnar, Tan, Qihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112246/
https://www.ncbi.nlm.nih.gov/pubmed/27909437
http://dx.doi.org/10.3389/fimmu.2016.00510
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author Svendsen, Anders J.
Gervin, Kristina
Lyle, Robert
Christiansen, Lene
Kyvik, Kirsten
Junker, Peter
Nielsen, Christian
Houen, Gunnar
Tan, Qihua
author_facet Svendsen, Anders J.
Gervin, Kristina
Lyle, Robert
Christiansen, Lene
Kyvik, Kirsten
Junker, Peter
Nielsen, Christian
Houen, Gunnar
Tan, Qihua
author_sort Svendsen, Anders J.
collection PubMed
description OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT. RESULTS: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated, and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment-naïve RA singletons. Gene-set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA. CONCLUSION: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA.
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spelling pubmed-51122462016-12-01 Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study Svendsen, Anders J. Gervin, Kristina Lyle, Robert Christiansen, Lene Kyvik, Kirsten Junker, Peter Nielsen, Christian Houen, Gunnar Tan, Qihua Front Immunol Immunology OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT. RESULTS: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated, and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment-naïve RA singletons. Gene-set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA. CONCLUSION: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA. Frontiers Media S.A. 2016-11-17 /pmc/articles/PMC5112246/ /pubmed/27909437 http://dx.doi.org/10.3389/fimmu.2016.00510 Text en Copyright © 2016 Svendsen, Gervin, Lyle, Christiansen, Kyvik, Junker, Nielsen, Houen and Tan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Svendsen, Anders J.
Gervin, Kristina
Lyle, Robert
Christiansen, Lene
Kyvik, Kirsten
Junker, Peter
Nielsen, Christian
Houen, Gunnar
Tan, Qihua
Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title_full Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title_fullStr Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title_full_unstemmed Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title_short Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis: An Epigenome-Wide Study
title_sort differentially methylated dna regions in monozygotic twin pairs discordant for rheumatoid arthritis: an epigenome-wide study
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112246/
https://www.ncbi.nlm.nih.gov/pubmed/27909437
http://dx.doi.org/10.3389/fimmu.2016.00510
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