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Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.ORCID-id: 0000-0002-2974-2003
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.ORCID-id: 0000-0002-6679-6414
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).ORCID-id: 0000-0002-9692-101x
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.ORCID-id: 0000-0001-8540-6891
2019 (Engelska)Ingår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, nr 7, s. 649-659Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

DNA methylation in blood may adapt to conditions affecting our health, such as inflammation, and multiple studies have identified differential DNA methylation related to smoking, obesity and various diseases. The purpose of this study was to evaluate previously reported, and explore possible new, associations between levels of inflammatory markers and DNA methylation in blood. We used a well-characterized study population consisting of 127 individuals, all of whom were participants in the population-based Vasterbotten Intervention Programme cohort and had provided two blood samples, ten years apart. Levels of CRP and 160 other proteins were measured in plasma, and DNA methylation levels (assessed using the 850K Illumina Infinium MethylationEPIC BeadChip) were measured in white blood cell DNA. Associations between CpG methylation and protein levels were estimated using linear mixed models. In the study we were able to confirm the direction for 85 of 102 previously reported protein-methylation associations. Depicting associations in a network allowed us to identify CpG sites with associations to multiple proteins, and ten CpG sites were each associated with three or more inflammatory markers. Furthermore, two genetic regions included nine additional unreported CpG sites that may represent trans-acting methylation sites. Our study supports a complex interaction between DNA methylation and circulating proteins involved in the inflammatory response. The notion of trans-acting methylation sites affecting, or being affected by, the expression of genes on completely different chromosomes should be taken into account when interpreting results from epigenome-wide association studies.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2019. Vol. 14, nr 7, s. 649-659
Nyckelord [en]
DNA methylation, inflammation, biomarkers, C, reactive protein, colorectal cancer, risk factors, epigenetics, proteomics
Nationell ämneskategori
Medicinsk genetik Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:umu:diva-160622DOI: 10.1080/15592294.2019.1603962ISI: 000470485500001PubMedID: 31033411OAI: oai:DiVA.org:umu-160622DiVA, id: diva2:1328220
Forskningsfinansiär
Västerbottens läns landsting, VLL-547711Västerbottens läns landsting, VLL-680921Västerbottens läns landstingTillgänglig från: 2019-06-20 Skapad: 2019-06-20 Senast uppdaterad: 2019-06-20Bibliografiskt granskad

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Myte, RobinSundkvist, Annelivan Guelpen, BethanyHarlid, Sophia
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OnkologiWallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
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Epigenetics
Medicinsk genetikMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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