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

Carola Marzi, Lesca M. Holdt, Giovanni Fiorito, Pei Chien Tsai, Anja Kretschmer, Simone Wahl, Simonetta Guarrera, Daniel Teupser, Timothy D. Spector, Licia Iacoviello, Carlotta Sacerdote, Konstantin Strauch, Serene Lee, Wolfgang E. Thasler, Annette Peters, Barbara Thorand, Petra Wolf, Holger Prokisch, Rosario Tumino, Christian GiegerVittorio Krogh, S. Panico, Jordana T. Bell, G. Matullo, Melanie Waldenberger, Harald Grallert, W. Koenig

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere0166015
JournalPLoS One
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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