Publication:
Methylation vs. protein inflammatory biomarkers and their associations with cardiovascular function

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dc.contributor.authorCronjé, H.T.
dc.contributor.authorElliott, H.R.
dc.contributor.authorNienaber-Rousseau, C.
dc.contributor.authorGreen, F.R.
dc.contributor.authorSchutte, A.E.
dc.contributor.authorPieters, M.
dc.contributor.departmentAletta E. Schutte: Hypertension in Africa Research Team, Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africaen_US
dc.date.accessioned2024-03-22T20:02:19Z
dc.date.available2024-03-22T20:02:19Z
dc.date.epub2020
dc.date.issued2020-07-31
dc.description.abstractDNA methylation data can be used to estimate proportions of leukocyte subsets retrospectively, when directly measured cell counts are unavailable. The methylation-derived neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios (mdNLRs and mdLMRs) have proven to be particularly useful as indicators of systemic inflammation. As with directly measured NLRs and LMRs, these methylation-derived ratios have been used as prognostic markers for cancer, although little is known about them in relation to other disorders with inflammatory components, such as cardiovascular disease (CVD). Recently, methylation of five genomic cytosine-phosphate-guanine sites (CpGs) was suggested as proxies for mdNLRs, potentially providing a cost-effective alternative when whole-genome methylation data are not available. This study compares seven methylation-derived inflammatory markers (mdNLR, mdLMR, and individual CpG sites) with five conventionally used protein-based inflammatory markers (C-reactive protein, interleukins 6 and 10, tumor-necrosis factor alpha, and interferon-gamma) and a protein-based inflammation score, in their associations with cardiovascular function (CVF) and risk. We found that markers of CVF were more strongly associated with methylation-derived than protein-based markers. In addition, the protein-based and methylation-derived inflammatory markers complemented rather than proxied one another in their contribution to the variance in CVF. There were no strong correlations between the methylation and protein markers either. Therefore, the methylation markers could offer unique information on the inflammatory process and are not just surrogate markers for inflammatory proteins. Although the five CpGs mirrored the mdNLR well in their capacity as proxies, they contributed to CVF above and beyond the mdNLR, suggesting possible added functional relevance. We conclude that methylation-derived indicators of inflammation enable individuals with increased CVD risk to be identified without measurement of protein-based inflammatory markers. In addition, the five CpGs investigated here could be useful surrogates for the NLR when the cost of array data cannot be met. Used in tandem, methylation-derived and protein-based inflammatory markers explain more variance than protein-based inflammatory markers alone.en_US
dc.description.sponsorshipThe PURE-SA-NW study was funded by the North-West University, South African National Research Foundation (SANRF), Population Health Research Institute, South African Medical Research Council (SAMRC).en_US
dc.identifier.citationCronjé HT, Elliott HR, Nienaber-Rousseau C, Green FR, Schutte AE, Pieters M. Methylation vs. Protein Inflammatory Biomarkers and Their Associations With Cardiovascular Function. Front Immunol. 2020 Jul 31;11:1577. doi: 10.3389/fimmu.2020.01577.en_US
dc.identifier.doi10.3389/fimmu.2020.01577
dc.identifier.journalFrontiers in Immunologyen_US
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411149/
dc.identifier.urihttps://hdl.handle.net/11288/595683
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.research.unitHypertension and Cardiovascular Diseaseen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectCell countsen_US
dc.subjectEpidemiologyen_US
dc.subjectEpigeneticsen_US
dc.subjectInflammationen_US
dc.subjectNeutrophil-to-lymphocyteen_US
dc.subjectLymphocyte-to-monocyteen_US
dc.subjectSDG-03 Good health and wll-beingen_US
dc.titleMethylation vs. protein inflammatory biomarkers and their associations with cardiovascular functionen_US
dc.typeArticleen_US
dspace.entity.typePublication
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