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DNA methylation and gene expression of HIF3A : cross-tissue validation and associations with BMI and insulin resistance

Main, Ailsa Maria; Gillberg, Linn LU ; Jacobsen, Anna Louisa; Nilsson, Emma LU ; Gjesing, Anette Prior; Hansen, Torben; Pedersen, Oluf; Ribel-Madsen, Rasmus and Vaag, Allan LU (2016) In Clinical Epigenetics 8(1).
Abstract

Background: Associations between BMI and DNA methylation of hypoxia-inducible factor 3-alpha (HIF3A) in both blood cells and subcutaneous adipose tissue (SAT) have been reported. In this study, we investigated associations between BMI and HIF3A DNA methylation in the blood and SAT from the same individuals, and whether HIF3A gene expression in SAT and skeletal muscle biopsies showed associations with BMI and insulin resistance. Furthermore, we aimed to investigate gender specificity and heritability of these traits. Methods: We studied 137 first-degree relatives of type 2 diabetes (T2D) patients from 48 families, from whom we had SAT and muscle biopsies. DNA methylation of four CpG sites in the HIF3A promoter was analyzed in the blood... (More)

Background: Associations between BMI and DNA methylation of hypoxia-inducible factor 3-alpha (HIF3A) in both blood cells and subcutaneous adipose tissue (SAT) have been reported. In this study, we investigated associations between BMI and HIF3A DNA methylation in the blood and SAT from the same individuals, and whether HIF3A gene expression in SAT and skeletal muscle biopsies showed associations with BMI and insulin resistance. Furthermore, we aimed to investigate gender specificity and heritability of these traits. Methods: We studied 137 first-degree relatives of type 2 diabetes (T2D) patients from 48 families, from whom we had SAT and muscle biopsies. DNA methylation of four CpG sites in the HIF3A promoter was analyzed in the blood and SAT by pyrosequencing, and HIF3A gene expression was analyzed in SAT and muscle by qPCR. An index of whole-body insulin sensitivity was estimated from oral glucose tolerance tests. Results: BMI was associated with HIF3A methylation at one CpG site in the blood, and there was a positive association between the blood and SAT methylation levels at a different CpG site within the individuals. The SAT methylation level did not correlate with HIF3A gene expression. Interestingly, HIF3A expression in SAT, but not in muscle, associated negatively with BMI and whole-body insulin resistance. We found a significant effect of familiality on HIF3A methylation levels in the blood and HIF3A expression levels in skeletal muscle. Conclusions: Our findings are in line with the previously reported link between BMI and DNA methylation of HIF3A in the blood. The tissue-specific results of HIF3A gene expression indicate that SAT is the more functional tissue in which a low expression may adversely affect whole-body insulin sensitivity.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epigenetics, Heritability, Insulin sensitivity, Obesity, Type 2 diabetes
in
Clinical Epigenetics
volume
8
issue
1
publisher
BioMed Central
external identifiers
  • Scopus:84984972704
ISSN
1868-7075
DOI
10.1186/s13148-016-0258-6
language
English
LU publication?
yes
id
41a42a5b-fbb0-407c-a795-361e3ae036a0
date added to LUP
2016-09-29 16:29:18
date last changed
2016-11-03 14:33:40
@misc{41a42a5b-fbb0-407c-a795-361e3ae036a0,
  abstract     = {<p>Background: Associations between BMI and DNA methylation of hypoxia-inducible factor 3-alpha (HIF3A) in both blood cells and subcutaneous adipose tissue (SAT) have been reported. In this study, we investigated associations between BMI and HIF3A DNA methylation in the blood and SAT from the same individuals, and whether HIF3A gene expression in SAT and skeletal muscle biopsies showed associations with BMI and insulin resistance. Furthermore, we aimed to investigate gender specificity and heritability of these traits. Methods: We studied 137 first-degree relatives of type 2 diabetes (T2D) patients from 48 families, from whom we had SAT and muscle biopsies. DNA methylation of four CpG sites in the HIF3A promoter was analyzed in the blood and SAT by pyrosequencing, and HIF3A gene expression was analyzed in SAT and muscle by qPCR. An index of whole-body insulin sensitivity was estimated from oral glucose tolerance tests. Results: BMI was associated with HIF3A methylation at one CpG site in the blood, and there was a positive association between the blood and SAT methylation levels at a different CpG site within the individuals. The SAT methylation level did not correlate with HIF3A gene expression. Interestingly, HIF3A expression in SAT, but not in muscle, associated negatively with BMI and whole-body insulin resistance. We found a significant effect of familiality on HIF3A methylation levels in the blood and HIF3A expression levels in skeletal muscle. Conclusions: Our findings are in line with the previously reported link between BMI and DNA methylation of HIF3A in the blood. The tissue-specific results of HIF3A gene expression indicate that SAT is the more functional tissue in which a low expression may adversely affect whole-body insulin sensitivity.</p>},
  author       = {Main, Ailsa Maria and Gillberg, Linn and Jacobsen, Anna Louisa and Nilsson, Emma and Gjesing, Anette Prior and Hansen, Torben and Pedersen, Oluf and Ribel-Madsen, Rasmus and Vaag, Allan},
  issn         = {1868-7075},
  keyword      = {Epigenetics,Heritability,Insulin sensitivity,Obesity,Type 2 diabetes},
  language     = {eng},
  month        = {09},
  number       = {1},
  publisher    = {ARRAY(0xb7a1bf8)},
  series       = {Clinical Epigenetics},
  title        = {DNA methylation and gene expression of HIF3A : cross-tissue validation and associations with BMI and insulin resistance},
  url          = {http://dx.doi.org/10.1186/s13148-016-0258-6},
  volume       = {8},
  year         = {2016},
}