Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood

作者: Tina Rönn , Petr Volkov , Linn Gillberg , Milana Kokosar , Alexander Perfilyev

DOI: 10.1093/HMG/DDV124

关键词: EndocrinologyBiologyKLF14DNA methylationEpigeneticsCandidate geneGeneticsMethylationAdipose tissueHIF3AInternal medicineGene

摘要: Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these on genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed ∼480,000 sites from 96 males 94 females, related to HbA1c. also compared epigenetic signatures blood. Age was significantly associated with both altered expression 1,050 genes (e.g. FHL2, NOX4 PLG). Interestingly, many reported biomarkers ageing blood, including ELOVL2, KLF14 GLRA1, showed significant correlations between age our study. The most association found upstream ELOVL2. identified 2,825 FTO, ITIH5, CCL18, MTCH2, IRS1 SPP1) where correlated BMI. Methylation at previously HIF3A females only. (range 28-46 mmol/mol) 711 sites, annotated e.g. RAB37, TICAM1 HLA-DPB1. Pathway analyses demonstrated that overrepresented among involved cancer, type 2 diabetes cardiovascular disease. Our results highlight variation candidate metabolic diseases cancer tissue. Importantly, we demonstrate blood can mirror age-related target tissues such as (Less)

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