Hypermethylated CpG Sites in the MTR Gene Promoter in Preterm Placenta

Abstract

Aim: Altered maternal one-carbon metabolism influences placental DNA methylation patterns and ‘programs’ the fetus for noncommunicable diseases in adult life. Experimental procedures: Levels of plasma folate, vitamin B₁₂, homocysteine, mRNA and protein levels of MTHFR and MTR enzymes in placenta were compared among women delivering preterm (n = 83) and term (n = 75). MTR promoter CpG methylation was undertaken. Results: MTHFR and MTR mRNA levels were higher while protein levels were lower, and MTR CpG sites were hypermethylated in the preterm group, as compared with the term group. Methylated CpG sites were negatively associated with maternal plasma vitamin B₁₂ levels. Conclusion: Study suggests a dysregulation of enzyme genes in remethylation arm of the one-carbon metabolism in placenta of women delivering preterm.

Keywords::

• DNA methylation
• epigenetics
• micronutrients
• MTHFR
• MTR
• one-carbon metabolism
• placenta
• preterm pregnancy
• remethylation pathway
• transcription factors

Acknowledgements

The authors are grateful to the participants for the successful completion of the study.

GR Chandak and SR Joshi conceived and designed the experiments. VV Khot performed majority of the experimental work with help from DK Yadav, L Kaur, V V Khot, DP Sundrani and S Shrestha carried out data analysis. VV Khot, PM Chavan-Gautam and SR Joshi wrote the paper with inputs from SS Mehendale, S Shrestha, L Kaur and GR Chandak.

Financial & competing interests disclosure

This work was supported by funds from Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India, India (VICYDIP). The authors acknowledge the Indian Council of Medical Research for giving the senior research fellowship (3/1/2/9/14/RCH) to one of the authors (VV Khot). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by funds from Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India, India (VICYDIP). The authors acknowledge the Indian Council of Medical Research for giving the senior research fellowship (3/1/2/9/14/RCH) to one of the authors (VV Khot). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.