title: 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.
abstract: Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of aging in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.
authors: Department of Clinical Sciences, Epigenetics and Diabetes and.
authors: Tina
authors: T
authors: Rönn
authors: Department of Clinical Sciences, Epigenetics and Diabetes and.
authors: Petr
authors: P
authors: Volkov
authors: Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors: Linn
authors: L
authors: Gillberg
authors: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 11, Box 434, 405 30 Gothenburg, Sweden.
authors: Milana
authors: M
authors: Kokosar
authors: Department of Clinical Sciences, Epigenetics and Diabetes and.
authors: Alexander
authors: A
authors: Perfilyev
authors: Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark.
authors: Anna Louisa
authors: AL
authors: Jacobsen
authors: Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark, Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark.
authors: Sine W
authors: SW
authors: Jørgensen
authors: Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark.
authors: Charlotte
authors: C
authors: Brøns
authors: Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Per-Anders
authors: PA
authors: Jansson
authors: Department of Clinical Sciences, Vascular Diseases, Lund University, 205 02 Malmö, Sweden.
authors: Karl-Fredrik
authors: KF
authors: Eriksson
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Universitetsparken 1, 2100 Copenhagen, Denmark and.
authors: Oluf
authors: O
authors: Pedersen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Universitetsparken 1, 2100 Copenhagen, Denmark and.
authors: Torben
authors: T
authors: Hansen
authors: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, CRC, 205 02 Malmö, Sweden.
authors: Leif
authors: L
authors: Groop
authors: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 11, Box 434, 405 30 Gothenburg, Sweden, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors: Elisabet
authors: E
authors: Stener-Victorin
authors: Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors: Allan
authors: A
authors: Vaag
authors: Department of Clinical Sciences, Epigenetics and Diabetes and Department of Endocrinology, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark.
authors: Emma
authors: E
authors: Nilsson
authors: Department of Clinical Sciences, Epigenetics and Diabetes and charlotte.ling@med.lu.se.
authors: Charlotte
authors: C
authors: Ling
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D055106:Genome-Wide Association Study; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013548:Sweden; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human