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Marzi, C. ; Holdt, L.M.* ; Fiorito, G.* ; Tsai, P.C.* ; Kretschmer, A. ; Wahl, S. ; Guarrera, S.* ; Teupser, D.* ; Spector, T.D.* ; Iacoviello, L.* ; Sacerdote, C.* ; Strauch, K. ; Lee, S.* ; Thasler, W.E.* ; Peters, A. ; Thorand, B. ; Wolf, P. ; Prokisch, H. ; Tumino, R.* ; Gieger, C. ; Krogh, V.* ; Panico, S.* ; Bell, J.T.* ; Matullo, G.* ; Waldenberger, M. ; Grallert, H. ; Koenig, W.*

Epigenetic signatures at AQP3 and SOCS3 engage in low-grade inflammation across different tissues.

PLoS ONE 11:e0166015 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Background Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. Results Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P ≤ 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/ STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels. Conclusions Epigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/ STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords C-reactive Protein; Dna Methylation Patterns; Promotes Cell-growth; Cardiovascular-disease; Cancer; Aquaporin-3; Blood; Atherosclerosis; Mechanisms; Leukocytes
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 11, Issue: 11, Pages: , Article Number: e0166015 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)