Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes
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Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes. / Nilsson, Emma; Jansson, Per Anders; Perfilyev, Alexander; Volkov, Petr; Pedersen, Maria; Svensson, Maria K; Poulsen, Pernille; Ribel-Madsen, Rasmus; Pedersen, Nancy L; Almgren, Peter; Fadista, João; Rönn, Tina; Klarlund Pedersen, Bente; Scheele, Camilla; Vaag, Allan; Ling, Charlotte.
In: Diabetes, Vol. 63, No. 9, 09.2014, p. 2962-2976.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes
AU - Nilsson, Emma
AU - Jansson, Per Anders
AU - Perfilyev, Alexander
AU - Volkov, Petr
AU - Pedersen, Maria
AU - Svensson, Maria K
AU - Poulsen, Pernille
AU - Ribel-Madsen, Rasmus
AU - Pedersen, Nancy L
AU - Almgren, Peter
AU - Fadista, João
AU - Rönn, Tina
AU - Klarlund Pedersen, Bente
AU - Scheele, Camilla
AU - Vaag, Allan
AU - Ling, Charlotte
N1 - © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
PY - 2014/9
Y1 - 2014/9
N2 - Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with control subjects. A total of 1,410 of these sites also showed differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified copy number variants (CNVs) in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.
AB - Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with control subjects. A total of 1,410 of these sites also showed differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified copy number variants (CNVs) in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.
KW - Adipose Tissue
KW - Aged
KW - Case-Control Studies
KW - Cohort Studies
KW - CpG Islands
KW - DNA Copy Number Variations
KW - DNA Methylation
KW - Diabetes Mellitus, Type 2
KW - Epigenesis, Genetic
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Panniculitis
KW - Transcriptome
KW - Twins, Monozygotic
U2 - 10.2337/db13-1459
DO - 10.2337/db13-1459
M3 - Journal article
C2 - 24812430
VL - 63
SP - 2962
EP - 2976
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 9
ER -
ID: 138419851