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Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes.

Dekker Nitert, Marloes LU ; Dayeh, Tasnim LU ; Volkov, Peter; Elgzyri, Targ LU ; Hall, Elin LU ; Nilsson, Emma LU ; Yang, Beatrice LU ; Lang, Stefan LU ; Parikh, Hemang LU and Wessman, Ylva LU , et al. (2012) In Diabetes
Abstract
To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential... (More)
To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH(+) men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH(+) and FH(-) individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 × 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome. (Less)
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Diabetes
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American Diabetes Association Inc.
external identifiers
  • wos:000312041700040
  • pmid:23028138
  • scopus:84870319843
ISSN
1939-327X
DOI
10.2337/db11-1653
language
English
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yes
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c7d2859b-99b3-4855-b0ec-9eaeb3839eaf (old id 3161277)
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http://www.ncbi.nlm.nih.gov/pubmed/23028138?dopt=Abstract
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2012-11-01 12:58:30
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2017-11-12 04:10:42
@article{c7d2859b-99b3-4855-b0ec-9eaeb3839eaf,
  abstract     = {To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH(+)) or without (FH(-)) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH(+) compared with FH(-) men. We further validated our findings from FH(+) men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH(+) men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH(+) and FH(-) individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P &lt; 3 × 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome.},
  author       = {Dekker Nitert, Marloes and Dayeh, Tasnim and Volkov, Peter and Elgzyri, Targ and Hall, Elin and Nilsson, Emma and Yang, Beatrice and Lang, Stefan and Parikh, Hemang and Wessman, Ylva and Weishaupt, Holger and Attema, Joanne and Abels, Mia and Wierup, Nils and Almgren, Peter and Jansson, Per-Anders and Rönn, Tina and Hansson, Ola and Eriksson, Karl-Fredrik and Groop, Leif and Ling, Charlotte},
  issn         = {1939-327X},
  language     = {eng},
  month        = {10},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes.},
  url          = {http://dx.doi.org/10.2337/db11-1653},
  year         = {2012},
}