Back to Search
Start Over
Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes.
- Source :
-
Diabetes [Diabetes] 2014 Sep; Vol. 63 (9), pp. 2962-76. Date of Electronic Publication: 2014 May 08. - Publication Year :
- 2014
-
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 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.<br /> (© 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.)
- Subjects :
- Adipose Tissue metabolism
Adipose Tissue pathology
Aged
Case-Control Studies
Cohort Studies
CpG Islands
DNA Copy Number Variations genetics
Delta-5 Fatty Acid Desaturase
Diabetes Mellitus, Type 2 genetics
Epigenesis, Genetic
Female
Humans
Male
Middle Aged
Panniculitis genetics
Twins, Monozygotic
DNA Methylation
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 63
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 24812430
- Full Text :
- https://doi.org/10.2337/db13-1459