P89 Epigenome-wide association study reveals differential DNA methylation in systemic lupus erythematosus patients with a history of ischemic heart disease

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10–1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05–4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41–4.18), ischemic heart disease (OR 3.39; 95% CI 2.08–5.54), systemic (OR 2.00; 95% CI 1.37–2.91), ocular (OR 1.58; 95% CI 1.16–2.14) and renal manifestations (OR 1.44; 95% CI 1.09–1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29–0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63–3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10–2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39–4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43–0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80–4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

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Association between ischemic heart disease and systemic lupus erythematosus—a large case-control study

Immunologic Research ◽

10.1007/s12026-016-8884-9 ◽

2017 ◽

Vol 65 (2) ◽

pp. 459-463 ◽

Cited By ~ 15

Author(s):

Abdulla Watad ◽

Arsalan Abu Much ◽

Danielle Bracco ◽

Naim Mahroum ◽

Doron Comaneshter ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Lupus Erythematosus ◽

Case Control Study ◽

Case Control ◽

Ischemic Heart ◽

Systemic Lupus ◽

Control Study ◽

Large Case

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Epigenome-wide association study of peripheral blood mononuclear cells in systemic lupus erythematosus: Identifying DNA methylation signatures associated with interferon-related genes based on ethnicity and SLEDAI

Journal of Autoimmunity ◽

10.1016/j.jaut.2018.09.007 ◽

2019 ◽

Vol 96 ◽

pp. 147-157 ◽

Cited By ~ 13

Author(s):

Stancy Joseph ◽

Nysia I. George ◽

Bridgett Green-Knox ◽

Edward L. Treadwell ◽

Beverly Word ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Dna Methylation ◽

Association Study ◽

Peripheral Blood Mononuclear Cells ◽

Lupus Erythematosus ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Systemic Lupus ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Genome-Wide Association Study in African-Americans with Systemic Lupus Erythematosus

10.21236/ada592038 ◽

2013 ◽

Author(s):

John Harley

Keyword(s):

Systemic Lupus Erythematosus ◽

African Americans ◽

Association Study ◽

Lupus Erythematosus ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Systemic Lupus ◽

Genome Wide

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Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study

Lupus ◽

10.1177/09612033211034559 ◽

2021 ◽

pp. 096120332110345

Author(s):

Stefan Vordenbäumen ◽

Alexander Sokolowski ◽

Anna Rosenbaum ◽

Claudia Gebhard ◽

Johanna Raithel ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Dna Methylation ◽

T Cells ◽

Disease Activity ◽

Lupus Erythematosus ◽

Cd40 Ligand ◽

Systemic Lupus ◽

Methyl Donors ◽

Methyl Donor ◽

The Mean

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

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Epigenetic Contribution and Genomic Imprinting Dlk1-Dio3 miRNAs in Systemic Lupus Erythematosus

Genes ◽

10.3390/genes12050680 ◽

2021 ◽

Vol 12 (5) ◽

pp. 680

Author(s):

Rujuan Dai ◽

Zhuang Wang ◽

S. Ansar Ahmed

Keyword(s):

Systemic Lupus Erythematosus ◽

Dna Methylation ◽

Lupus Erythematosus ◽

Critical Role ◽

Methylation Status ◽

Transcriptional Level ◽

Dna Hypomethylation ◽

Systemic Lupus ◽

Multiple Organs ◽

Genetic Imprinting

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that afflicts multiple organs, especially kidneys and joints. In addition to genetic predisposition, it is now evident that DNA methylation and microRNAs (miRNAs), the two major epigenetic modifications, are critically involved in the pathogenesis of SLE. DNA methylation regulates promoter accessibility and gene expression at the transcriptional level by adding a methyl group to 5′ cytosine within a CpG dinucleotide. Extensive evidence now supports the importance of DNA hypomethylation in SLE etiology. miRNAs are small, non-protein coding RNAs that play a critical role in the regulation of genome expression. Various studies have identified the signature lupus-related miRNAs and their functional contribution to lupus incidence and progression. In this review, the mutual interaction between DNA methylation and miRNAs regulation in SLE is discussed. Some lupus-associated miRNAs regulate DNA methylation status by targeting the DNA methylation enzymes or methylation pathway-related proteins. On the other hand, DNA hyper- and hypo-methylation are linked with dysregulated miRNAs expression in lupus. Further, we specifically discuss the genetic imprinting Dlk1-Dio3 miRNAs that are subjected to DNA methylation regulation and are dysregulated in several autoimmune diseases, including SLE.

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