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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 A LU ; Jansson, Per Anders; Perfilyev, Alexander LU ; Volkov, Petr LU ; Pedersen, Maria; Svensson, Maria K; Poulsen, Pernille; Ribel-Madsen, Rasmus; Pedersen, Nancy L and Almgren, Peter LU , et al. (2014) In Diabetes 63(9). p.2962-2976
Abstract
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 discordant 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... (More)
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 discordant 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 controls. 1,410 of these sites did also show differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified 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. (Less)
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Contribution to journal
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published
subject
in
Diabetes
volume
63
issue
9
pages
2962 - 2976
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:24812430
  • wos:000341505300014
  • scopus:84906707442
ISSN
1939-327X
DOI
10.2337/db13-1459
language
English
LU publication?
yes
id
38cbfe41-5064-4c25-96e0-219816d5c09d (old id 4455578)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24812430?dopt=Abstract
date added to LUP
2014-06-03 22:32:56
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2017-11-12 03:04:15
@article{38cbfe41-5064-4c25-96e0-219816d5c09d,
  abstract     = {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 discordant 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 controls. 1,410 of these sites did also show differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified 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.},
  author       = {Nilsson, Emma A and Jansson, Per Anders and Perfilyev, Alexander and Volkov, Petr and Pedersen, Maria and Svensson, Maria K and Poulsen, Pernille and Ribel-Madsen, Rasmus and Pedersen, Nancy L and Almgren, Peter and Fadista, Joao and Rönn, Tina and Klarlund-Pedersen, Bente and Scheele, Camilla and Vaag, Allan and Ling, Charlotte},
  issn         = {1939-327X},
  language     = {eng},
  number       = {9},
  pages        = {2962--2976},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes.},
  url          = {http://dx.doi.org/10.2337/db13-1459},
  volume       = {63},
  year         = {2014},
}