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Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.
Hjort, Line; Bredgaard, Sandra Stokholm; Manitta, Eleonora; Marques, Irene; Sørensen, Anja Elaine; Martino, David; Grunnet, Louise Groth; Kelstrup, Louise; Houshmand-Oeregaard, Azadeh; Clausen, Tine Dalsgaard; Mathiesen, Elisabeth Reinhardt; Olsen, Sjurdur Frodi; Saffery, Richard; Barrès, Romain; Damm, Peter; Vaag, Allan Arthur; Dalgaard, Louise Torp.
Afiliación
  • Hjort L; Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Epigenetics Group, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. line.hjort@sund.ku.dk.
  • Bredgaard SS; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. line.hjort@sund.ku.dk.
  • Manitta E; Department of Science and Environment, Roskilde University, Roskilde, Denmark.
  • Marques I; Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Epigenetics Group, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Sørensen AE; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Martino D; Department of Science and Environment, Roskilde University, Roskilde, Denmark.
  • Grunnet LG; Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia.
  • Kelstrup L; Wal-Yan Respiratory Research Centre, Telethon Kids Institute, Perth Children's Hospital, Nedlands, WA, Australia.
  • Houshmand-Oeregaard A; Clinical Research, Steno Diabetes Center Copenhagen, Herlev Hospital, Herlev, Denmark.
  • Clausen TD; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Mathiesen ER; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Olsen SF; Department of Gynecology and Obstetrics, Herlev Hospital, Herlev, Denmark.
  • Saffery R; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Barrès R; Novo Nordisk A/S, Bagsværd, Denmark.
  • Damm P; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Vaag AA; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Dalgaard LT; Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
Clin Epigenetics ; 16(1): 61, 2024 May 07.
Article en En | MEDLINE | ID: mdl-38715048
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Tejido Adiposo / Diabetes Gestacional / Músculo Esquelético / Metilación de ADN / Epigénesis Genética Límite: Adolescent / Adult / Child / Female / Humans / Male / Pregnancy Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Tejido Adiposo / Diabetes Gestacional / Músculo Esquelético / Metilación de ADN / Epigénesis Genética Límite: Adolescent / Adult / Child / Female / Humans / Male / Pregnancy Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Alemania