A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients
Coit P, Ortiz-Fernandez L, Lewis EE, McCune WJ, Maksimowicz-McKinnon K, and Sawalha AH. A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients. JCI Insight 2020.
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 two 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 interferon-response genes such as IRF7 and IFI44, and genes related to the NFkB pathway. TREML4, which plays a vital role in toll-like receptor signaling, was hypomethylated in African-American patients and demonstrated a strong cis-meQTL effect among 8855 cis-meQTL associations identified in our study.
ePub ahead of print