| Title: |
A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| Authors: |
Patrick Coit, Lourdes Ortiz-Fernandez, Emily E. Lewis, W. Joseph McCune, Kathleen Maksimowicz-McKinnon, Amr H. Sawalha |
| Source: |
JCI Insight, Vol 5, Iss 22 (2020) |
| Publisher Information: |
American Society for Clinical investigation, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Autoimmunity, Medicine |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2379-3708 |
| Relation: |
https://doaj.org/toc/2379-3708 |
| DOI: |
10.1172/jci.insight.143654 |
| Access URL: |
https://doaj.org/article/9bde268ed6c2483eb816f978eb9ea2a9 |
| Accession Number: |
edsdoj.9bde268ed6c2483eb816f978eb9ea2a9 |
| Database: |
Directory of Open Access Journals |
