TY - JOUR
T1 - Epigenetic signatures at AQP3 and SOCS3 engage in low-grade inflammation across different tissues
AU - Marzi, Carola
AU - Holdt, Lesca M.
AU - Fiorito, Giovanni
AU - Tsai, Pei Chien
AU - Kretschmer, Anja
AU - Wahl, Simone
AU - Guarrera, Simonetta
AU - Teupser, Daniel
AU - Spector, Tim D.
AU - Iacoviello, Licia
AU - Sacerdote, Carlotta
AU - Strauch, Konstantin
AU - Lee, Serene
AU - Thasler, Wolfgang E.
AU - Peters, Annette
AU - Thorand, Barbara
AU - Wolf, Petra
AU - Prokisch, Holger
AU - Tumino, Rosario
AU - Gieger, Christian
AU - Krogh, Vittorio
AU - Panico, Salvatore
AU - Bell, Jordana T.
AU - Matullo, Giuseppe
AU - Waldenberger, Melanie
AU - Grallert, Harald
AU - Koenig, Wolfgang
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84994632719&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0166015
DO - 10.1371/journal.pone.0166015
M3 - Article
AN - SCOPUS:84994632719
SN - 1932-6203
VL - 11
JO - PL o S One
JF - PL o S One
IS - 11
M1 - e0166015
ER -