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Epigenetics of the ...
Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy
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- Hjort, Line (författare)
- Novo Nordisk Foundation Centre for Basic Metabolic Research,Copenhagen University Hospital
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- Bredgaard, Sandra Stokholm (författare)
- Zealand University Hospital
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- Manitta, Eleonora (författare)
- Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Marques, Irene (författare)
- Copenhagen University Hospital
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- Sørensen, Anja Elaine (författare)
- Zealand University Hospital
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- Martino, David (författare)
- Murdoch Children's Research Institute,Perth Children’s Hospital
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- Grunnet, Louise Groth (författare)
- Steno Diabetes Center Copenhagen
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- Kelstrup, Louise (författare)
- Copenhagen University Hospital,Gentofte Hospital,University of Copenhagen
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- Houshmand-Oeregaard, Azadeh (författare)
- Novo Nordisk A/S,Copenhagen University Hospital
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- Clausen, Tine Dalsgaard (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Mathiesen, Elisabeth Reinhardt (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Olsen, Sjurdur Frodi (författare)
- Danish Serum Institute, Copenhagen
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- Saffery, Richard (författare)
- University of Melbourne,Murdoch Children's Research Institute
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- Barrès, Romain (författare)
- Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Damm, Peter (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Vaag, Allan Arthur (författare)
- Lund University,Lunds universitet,Translationell diabetesforskning,Forskargrupper vid Lunds universitet,Translational Diabetes Research,Lund University Research Groups,Steno Diabetes Center Copenhagen
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- Dalgaard, Louise Torp (författare)
- Zealand University Hospital
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: Clinical Epigenetics. - 1868-7075. ; 16:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Adipose
- Developmental programming
- DNA methylation
- Epigenetics
- Gene expression
- Gestational diabetes
- Intrauterine hyperglycemia
- Muscle
- nc886
- ncRNA
- Type 1 diabetes
- VTRNA2-1
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Hjort, Line
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Bredgaard, Sandr ...
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Manitta, Eleonor ...
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Marques, Irene
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Sørensen, Anja E ...
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Martino, David
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Grunnet, Louise ...
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Kelstrup, Louise
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Houshmand-Oerega ...
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Clausen, Tine Da ...
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Mathiesen, Elisa ...
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Olsen, Sjurdur F ...
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Saffery, Richard
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Barrès, Romain
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Damm, Peter
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Vaag, Allan Arth ...
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Dalgaard, Louise ...
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