Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?

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Standard

Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes? / Gillberg, Linn; Jacobsen, Stine; Ribel-Madsen, Rasmus; Gjesing, Anette Marianne Prior; Boesgaard, Trine W; Ling, Charlotte; Pedersen, Oluf; Hansen, Torben; Vaag, Allan.

In: P L o S One, Vol. 8, No. 3, 2013, p. e58384.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gillberg, L, Jacobsen, S, Ribel-Madsen, R, Gjesing, AMP, Boesgaard, TW, Ling, C, Pedersen, O, Hansen, T & Vaag, A 2013, 'Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?', P L o S One, vol. 8, no. 3, pp. e58384. https://doi.org/10.1371/journal.pone.0058384, https://doi.org/10.1371/annotation/5c3cf392-57b5-4e80-9a66-4997d10200ae

APA

Gillberg, L., Jacobsen, S., Ribel-Madsen, R., Gjesing, A. M. P., Boesgaard, T. W., Ling, C., Pedersen, O., Hansen, T., & Vaag, A. (2013). Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes? P L o S One, 8(3), e58384. https://doi.org/10.1371/journal.pone.0058384, https://doi.org/10.1371/annotation/5c3cf392-57b5-4e80-9a66-4997d10200ae

Vancouver

Gillberg L, Jacobsen S, Ribel-Madsen R, Gjesing AMP, Boesgaard TW, Ling C et al. Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes? P L o S One. 2013;8(3):e58384. https://doi.org/10.1371/journal.pone.0058384, https://doi.org/10.1371/annotation/5c3cf392-57b5-4e80-9a66-4997d10200ae

Author

Gillberg, Linn ; Jacobsen, Stine ; Ribel-Madsen, Rasmus ; Gjesing, Anette Marianne Prior ; Boesgaard, Trine W ; Ling, Charlotte ; Pedersen, Oluf ; Hansen, Torben ; Vaag, Allan. / Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?. In: P L o S One. 2013 ; Vol. 8, No. 3. pp. e58384.

Bibtex

@article{9d94c65458a34bef8b6c5ba34cd33328,
title = "Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?",
abstract = "Epigenetics may play a role in the pathophysiology of type 2 diabetes (T2D), and increased DNA methylation of the metabolic master regulator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) has been reported in muscle and pancreatic islets from T2D patients and in muscle from individuals at risk of T2D. This study aimed to investigate DNA promoter methylation and gene expression of PPARGC1A in skeletal muscle from first degree relatives (FDR) of T2D patients, and to determine the association with insulin action as well as the influence of family relation. We included 124 Danish FDR of T2D patients from 46 different families. Skeletal muscle biopsies were excised from vastus lateralis and insulin action was assessed by oral glucose tolerance tests. DNA methylation and mRNA expression levels were measured using bisulfite sequencing and quantitative real-time PCR, respectively. The average PPARGC1A methylation at four CpG sites situated 867-624 bp from the transcription start was associated with whole-body insulin sensitivity in a paradoxical positive manner ({\ss}¿=¿0.12, P¿=¿0.03), supported by a borderline significant inverse correlation with fasting insulin levels ({\ss}¿=¿-0.88, P¿=¿0.06). Excluding individuals with prediabetes and overt diabetes did not affect the overall result. DNA promoter methylation was not associated with PPARGC1A gene expression. The familiality estimate of PPARGC1A gene expression was high (h(2) ¿=¿79±27% (h(2) ±SE), P¿=¿0.002), suggesting genetic regulation to play a role. No significant effect of familiality on DNA methylation was found. Taken together, increased DNA methylation of the PPARGC1A promoter is unlikely to play a major causal role for the development of insulin resistance in FDR of patients with T2D.",
author = "Linn Gillberg and Stine Jacobsen and Rasmus Ribel-Madsen and Gjesing, {Anette Marianne Prior} and Boesgaard, {Trine W} and Charlotte Ling and Oluf Pedersen and Torben Hansen and Allan Vaag",
note = "Correction incl.",
year = "2013",
doi = "10.1371/journal.pone.0058384",
language = "English",
volume = "8",
pages = "e58384",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?

AU - Gillberg, Linn

AU - Jacobsen, Stine

AU - Ribel-Madsen, Rasmus

AU - Gjesing, Anette Marianne Prior

AU - Boesgaard, Trine W

AU - Ling, Charlotte

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Vaag, Allan

N1 - Correction incl.

PY - 2013

Y1 - 2013

N2 - Epigenetics may play a role in the pathophysiology of type 2 diabetes (T2D), and increased DNA methylation of the metabolic master regulator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) has been reported in muscle and pancreatic islets from T2D patients and in muscle from individuals at risk of T2D. This study aimed to investigate DNA promoter methylation and gene expression of PPARGC1A in skeletal muscle from first degree relatives (FDR) of T2D patients, and to determine the association with insulin action as well as the influence of family relation. We included 124 Danish FDR of T2D patients from 46 different families. Skeletal muscle biopsies were excised from vastus lateralis and insulin action was assessed by oral glucose tolerance tests. DNA methylation and mRNA expression levels were measured using bisulfite sequencing and quantitative real-time PCR, respectively. The average PPARGC1A methylation at four CpG sites situated 867-624 bp from the transcription start was associated with whole-body insulin sensitivity in a paradoxical positive manner (߿=¿0.12, P¿=¿0.03), supported by a borderline significant inverse correlation with fasting insulin levels (߿=¿-0.88, P¿=¿0.06). Excluding individuals with prediabetes and overt diabetes did not affect the overall result. DNA promoter methylation was not associated with PPARGC1A gene expression. The familiality estimate of PPARGC1A gene expression was high (h(2) ¿=¿79±27% (h(2) ±SE), P¿=¿0.002), suggesting genetic regulation to play a role. No significant effect of familiality on DNA methylation was found. Taken together, increased DNA methylation of the PPARGC1A promoter is unlikely to play a major causal role for the development of insulin resistance in FDR of patients with T2D.

AB - Epigenetics may play a role in the pathophysiology of type 2 diabetes (T2D), and increased DNA methylation of the metabolic master regulator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) has been reported in muscle and pancreatic islets from T2D patients and in muscle from individuals at risk of T2D. This study aimed to investigate DNA promoter methylation and gene expression of PPARGC1A in skeletal muscle from first degree relatives (FDR) of T2D patients, and to determine the association with insulin action as well as the influence of family relation. We included 124 Danish FDR of T2D patients from 46 different families. Skeletal muscle biopsies were excised from vastus lateralis and insulin action was assessed by oral glucose tolerance tests. DNA methylation and mRNA expression levels were measured using bisulfite sequencing and quantitative real-time PCR, respectively. The average PPARGC1A methylation at four CpG sites situated 867-624 bp from the transcription start was associated with whole-body insulin sensitivity in a paradoxical positive manner (߿=¿0.12, P¿=¿0.03), supported by a borderline significant inverse correlation with fasting insulin levels (߿=¿-0.88, P¿=¿0.06). Excluding individuals with prediabetes and overt diabetes did not affect the overall result. DNA promoter methylation was not associated with PPARGC1A gene expression. The familiality estimate of PPARGC1A gene expression was high (h(2) ¿=¿79±27% (h(2) ±SE), P¿=¿0.002), suggesting genetic regulation to play a role. No significant effect of familiality on DNA methylation was found. Taken together, increased DNA methylation of the PPARGC1A promoter is unlikely to play a major causal role for the development of insulin resistance in FDR of patients with T2D.

U2 - 10.1371/journal.pone.0058384

DO - 10.1371/journal.pone.0058384

M3 - Journal article

C2 - 23505498

VL - 8

SP - e58384

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

ER -

ID: 44880431