Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

Helen R. Gosselt; Costanza L. Vallerga; Pooja R. Mandaviya; Erik Lubberts; Johanna M.W. Hazes; Robert De Jonge; Sandra G. Heil

doi:10.1371/journal.pone.0247709

Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

Helen R. Gosselt^*, Costanza L. Vallerga, Pooja R. Mandaviya, Erik Lubberts, Johanna M.W. Hazes, Robert De Jonge, Sandra G. Heil

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Aim To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. Materials and methods DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months. Results Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs. Conclusion No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-Analyses are required.

Original language	English
Article number	e0247709
Journal	PLoS ONE
Volume	16
Issue number	3 March
DOIs	https://doi.org/10.1371/journal.pone.0247709
Publication status	Published - Mar 2021

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title = "Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients",

abstract = "Aim To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. Materials and methods DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months. Results Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs. Conclusion No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-Analyses are required.",

author = "Gosselt, {Helen R.} and Vallerga, {Costanza L.} and Mandaviya, {Pooja R.} and Erik Lubberts and Hazes, {Johanna M.W.} and {De Jonge}, Robert and Heil, {Sandra G.}",

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month = mar,

doi = "10.1371/journal.pone.0247709",

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volume = "16",

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T1 - Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

AU - Gosselt, Helen R.

AU - Vallerga, Costanza L.

AU - Mandaviya, Pooja R.

AU - Lubberts, Erik

AU - Hazes, Johanna M.W.

AU - De Jonge, Robert

AU - Heil, Sandra G.

PY - 2021/3

Y1 - 2021/3

N2 - Aim To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. Materials and methods DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months. Results Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs. Conclusion No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-Analyses are required.

AB - Aim To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. Materials and methods DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months. Results Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs. Conclusion No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-Analyses are required.

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Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

Abstract

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