A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients.
Adolescent
Adult
Black or African American
/ genetics
Aged
Biomarkers
/ analysis
Case-Control Studies
DNA Methylation
Epigenesis, Genetic
Female
Genome-Wide Association Study
Humans
Interferon Regulatory Factor-7
/ genetics
Longitudinal Studies
Lupus Nephritis
/ genetics
Middle Aged
Prognosis
Quantitative Trait Loci
Receptors, Immunologic
/ genetics
Signal Transduction
Sorting Nexins
/ genetics
White People
/ genetics
Young Adult
Autoimmunity
Epigenetics
Lupus
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
19 11 2020
19 11 2020
Historique:
received:
25
08
2020
accepted:
14
10
2020
pubmed:
28
10
2020
medline:
8
6
2021
entrez:
27
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33108347
pii: 143654
doi: 10.1172/jci.insight.143654
pmc: PMC7710270
doi:
pii:
Substances chimiques
Biomarkers
0
IRF7 protein, human
0
Interferon Regulatory Factor-7
0
Receptors, Immunologic
0
SNX18 protein, human
0
Sorting Nexins
0
TREML4 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI097134
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI110502
Pays : United States
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