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DNA methylation in the pathogenesis of type 2 diabetes in humans

Davegårdh, Cajsa LU ; García-Calzón, Sonia LU ; Bacos, Karl LU and Ling, Charlotte LU (2018) In Molecular Metabolism
Abstract

Background: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D. Scope of Review: This review summarizes knowledge of the impact of epigenetics on the pathogenesis of T2D in humans. In particular,... (More)

Background: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D. Scope of Review: This review summarizes knowledge of the impact of epigenetics on the pathogenesis of T2D in humans. In particular, the review will focus on alterations in DNA methylation in four human tissues of importance for the disease; pancreatic islets, skeletal muscle, adipose tissue, and the liver. Case-control studies and studies examining the impact of non-genetic and genetic risk factors on DNA methylation in humans will be considered. These studies identified epigenetic changes in tissues from subjects with T2D versus non-diabetic controls. They also demonstrate that non-genetic factors associated with T2D such as age, obesity, energy rich diets, physical activity and the intrauterine environment impact the epigenome in humans. Additionally, interactions between genetics and epigenetics seem to influence the pathogenesis of T2D. Conclusions: Overall, previous studies by our group and others support a key role for epigenetics in the growing incidence of T2D.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
DNA methylation, Epigenetics, Type 2 diabetes
in
Molecular Metabolism
publisher
Elsevier GmbH
external identifiers
  • scopus:85042586000
ISSN
2212-8778
DOI
10.1016/j.molmet.2018.01.022
language
English
LU publication?
yes
id
7af7191b-c6fb-4304-a003-4b5f44e4dfaf
date added to LUP
2018-03-09 08:05:56
date last changed
2018-06-24 05:21:05
@article{7af7191b-c6fb-4304-a003-4b5f44e4dfaf,
  abstract     = {<p>Background: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D. Scope of Review: This review summarizes knowledge of the impact of epigenetics on the pathogenesis of T2D in humans. In particular, the review will focus on alterations in DNA methylation in four human tissues of importance for the disease; pancreatic islets, skeletal muscle, adipose tissue, and the liver. Case-control studies and studies examining the impact of non-genetic and genetic risk factors on DNA methylation in humans will be considered. These studies identified epigenetic changes in tissues from subjects with T2D versus non-diabetic controls. They also demonstrate that non-genetic factors associated with T2D such as age, obesity, energy rich diets, physical activity and the intrauterine environment impact the epigenome in humans. Additionally, interactions between genetics and epigenetics seem to influence the pathogenesis of T2D. Conclusions: Overall, previous studies by our group and others support a key role for epigenetics in the growing incidence of T2D.</p>},
  author       = {Davegårdh, Cajsa and García-Calzón, Sonia and Bacos, Karl and Ling, Charlotte},
  issn         = {2212-8778},
  keyword      = {DNA methylation,Epigenetics,Type 2 diabetes},
  language     = {eng},
  month        = {02},
  publisher    = {Elsevier GmbH},
  series       = {Molecular Metabolism},
  title        = {DNA methylation in the pathogenesis of type 2 diabetes in humans},
  url          = {http://dx.doi.org/10.1016/j.molmet.2018.01.022},
  year         = {2018},
}