A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients
Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in...
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2020-11-01
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doaj-9bde268ed6c2483eb816f978eb9ea2a92021-08-02T15:56:06ZengAmerican Society for Clinical investigationJCI Insight2379-37082020-11-01522A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patientsPatrick CoitLourdes Ortiz-FernandezEmily E. LewisW. Joseph McCuneKathleen Maksimowicz-McKinnonAmr H. SawalhaEpigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time. DNA methylation levels in 2 CpG sites correlated significantly with changes in lupus disease activity. Progressive demethylation in SNX18 was observed with increasing disease activity in African American patients. Importantly, demethylation of a CpG site located within GALNT18 was associated with the development of active lupus nephritis. Differentially methylated genes between African American and European American lupus patients include type I IFN–response genes such as IRF7 and IFI44, and genes related to the NF-κB pathway. TREML4, which plays a vital role in TLR signaling, was hypomethylated in African American patients and demonstrated a strong cis–methylation quantitative trait loci (cis-meQTL) effect among 8855 cis-meQTL associations identified in our study.https://doi.org/10.1172/jci.insight.143654Autoimmunity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha |
spellingShingle |
Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients JCI Insight Autoimmunity |
author_facet |
Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha |
author_sort |
Patrick Coit |
title |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
title_short |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
title_full |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
title_fullStr |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
title_full_unstemmed |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
title_sort |
longitudinal and transancestral analysis of dna methylation patterns and disease activity in lupus patients |
publisher |
American Society for Clinical investigation |
series |
JCI Insight |
issn |
2379-3708 |
publishDate |
2020-11-01 |
description |
Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time. DNA methylation levels in 2 CpG sites correlated significantly with changes in lupus disease activity. Progressive demethylation in SNX18 was observed with increasing disease activity in African American patients. Importantly, demethylation of a CpG site located within GALNT18 was associated with the development of active lupus nephritis. Differentially methylated genes between African American and European American lupus patients include type I IFN–response genes such as IRF7 and IFI44, and genes related to the NF-κB pathway. TREML4, which plays a vital role in TLR signaling, was hypomethylated in African American patients and demonstrated a strong cis–methylation quantitative trait loci (cis-meQTL) effect among 8855 cis-meQTL associations identified in our study. |
topic |
Autoimmunity |
url |
https://doi.org/10.1172/jci.insight.143654 |
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