Altered SOCS3 DNA methylation within exon 2 is associated with increased mRNA expression in visceral adipose tissue in gestational diabetes

ABSTRACT

Overweight/obesity is the main risk factor for gestational diabetes mellitus (GDM). In our cohort of pregnant women with GDM, n = 19, and without, n = 22, we previously reported a significant increase in SOCS3 mRNA expression (+62%) in visceral adipose tissue (VAT) according to GDM, without altered promoter DNA-methylation. Here, we examined methylation status of additional SOCS3 exon 2 regions in VAT and maternal blood. We found significantly altered methylation at specific CpG sites corresponding to aberrant mRNA expression levels of SOCS3 in VAT. We propose a potential regulatory element/region within exon 2; however, this region does not appear to be a good blood-marker representing VAT.

KEYWORDS:

• Gestational diabetes mellitus
• epigenetics
• DNA methylation
• SOCS3
• adipose tissue
• maternal blood

Acknowledgments

The authors acknowledge Jens Stupin, MD, Joachim W. Dudenhausen, MD, PhD, FRCOG, Thomas Harder, MD, Andrea Loui, MD, Elisabeth Eilers, MD, and Sandra Schulz, MSc, for contributions to initial study cohort design, subject recruitment, and/or sample/data collection, respectively. We are very grateful to all study participants as well as the midwives and staff of the Clinic of Obstetrics at the Charité, Campus Virchow-Klinikum, Berlin, Germany, for the support in recruitment and sample/data collection.

Authors’ contributions

RCR contributed to design and conceptualization of the study, performed experiments, analyzed and interpreted the data and wrote the original draft. RO contributed to design and conceptualization of the study, performed experiments, analyzed the data, and reviewed the final draft. KS contributed to data collection/management and interpretation and reviewed the final manuscript. TZ performed laboratory measurements and reviewed the final manuscript. KM was involved in data collection/management and laboratory measurements and reviewed the final draft. WH provided resources and reviewed the final draft. AP contributed to design and conceptualization of the study, analyzed, and interpreted the data and wrote the original draft. All authors critically read and approved the final manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Ethical approval and consent to participate

Research design and methods were conducted in accordance with the Declaration of Helsinki, revised in 2004, and approved by the local Ethics Committee (Ethikausschuss 2 am Campus Virchow-Klinikum, Charité – Universitätsklinikum Berlin, EA2/026/04). All participants provided written informed consent before inclusion into the study.

Consent for publication

Not applicable.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on rational request.

Additional information

Funding

This study was supported in part by grants of the German Research Foundation [DFG: PL-241/5-1, GRK 1208] to Dr Plagemann. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.