Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes

Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. We aimed to examine whether global DNA methylation differences exist in major glucose metabolic tissues from these twins. Skeletal muscle (n = 11 pairs) and subc...

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Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e51302
Main Authors: Ribel-Madsen, Rasmus, Fraga, Mario F, Jacobsen, Stine, Bork-Jensen, Jette, Lara, Ester, Calvanese, Vincenzo, Fernandez, Agustin F, Friedrichsen, Martin, Vind, Birgitte F, Højlund, Kurt, Beck-Nielsen, Henning, Esteller, Manel, Vaag, Allan, Poulsen, Pernille
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose Tissue - metabolism
Biology
Bisulfite
Body mass
Body mass index
Body size
CpG islands
Cytosine
Deoxyribonucleic acid
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
DNA
DNA Methylation
DNA microarrays
DNA sequencing
Epigenetics
Gene sequencing
Genes
Genome-Wide Association Study
Genomes
Genomics
Glucose
Glucose metabolism
Guanine
Hepatocyte nuclear factor 4
Humans
Insulin resistance
Kinases
Medicine
Methylation
Muscle, Skeletal - metabolism
Muscles
Nucleotide sequence
Promoters
Purines
Pyrimidines
Skeletal muscle
Sulfites
Tissues
Twins
Twins, Monozygotic
Type 2 diabetes
Variation
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Summary:Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. We aimed to examine whether global DNA methylation differences exist in major glucose metabolic tissues from these twins. Skeletal muscle (n = 11 pairs) and subcutaneous adipose tissue (n = 5 pairs) biopsies were collected from 53-80 year-old monozygotic twin pairs discordant for type 2 diabetes. DNA methylation was measured by microarrays at 26,850 cytosine-guanine dinucleotide (CpG) sites in the promoters of 14,279 genes. Bisulfite sequencing was applied to validate array data and to quantify methylation of intergenic repetitive DNA sequences. The overall intra-pair variation in DNA methylation was large in repetitive (LINE1, D4Z4 and NBL2) regions compared to gene promoters (standard deviation of intra-pair differences: 10% points vs. 4% points, P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0051302