期刊
HUMAN MOLECULAR GENETICS
卷 25, 期 4, 页码 817-827出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddv511
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资金
- Swedish Medical Research Council [2011-2354, K2007-66X-20270-01-3]
- Goran Gustafssons Foundation
- Foundation for Strategic Research (SSF)
- European Commission [01947 (LSHG-CT-2006-01947)]
- Swedish Society for Medical Research (SSMF)
- Kjell och Marta Beijers Foundation
- Marcus Borgstrom Foundation
- AkeWiberg foundation
- Vleugels Foundation
- Wellcome Trust [WT098017]
Growth-differentiation factor 15 (GDF-15) is expressed in low to moderate levels in most healthy tissues and increases in response to inflammation. GDF-15 is associated with cardiovascular dysfunction and over-expressed in the myocardium of patients with myocardial infarction (MI). However, little is known about the function of GDF-15 in cardiovascular disease, and the underlying regulatory network of GDF-15 is not known. To investigate a possible association between GDF-15 levels and DNA methylation, we performed a genome-wide DNA methylation study of white blood cells in a population-based study (N = 717). Significant loci where replicated in an independent cohort (N = 963). We also performed a gene ontology (GO) enrichment analysis. We identified and replicated 16 CpG-sites (false discovery rate [FDR] < 0.05), at 11 independent loci including MIR21. MIR21 encodes a microRNA (miR-21) that has previously been shown to be associated with the development of heart disease. Interestingly, GDF15 mRNA contains a binding site for miR-21. Four sites were also differentially methylated in blood from participants previously diagnosed with MI and 14 enriched GO terms (FDR < 0.05, enrichment > 2) were identified, including 'cardiac muscle cell differentiation'. This study shows that GDF-15 levels are associated with differences in DNA methylation in blood cells, and a subset of the loci are also differentially methylated in participants with MI. However, there might be interactions between GDF-15 levels and methylation in other tissues not addressed in this study. These results provide novel links between GDF-15 and cardiovascular disease.
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