Hypermethylated CpG sites in the MTR gene promoter in preterm placenta

Epigenomics. 2017 Jul;9(7):985-996. doi: 10.2217/epi-2016-0173. Epub 2017 Jun 15.

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; MTHFR; MTR; epigenetics; micronutrients; one-carbon metabolism; placenta; preterm pregnancy; remethylation pathway; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / blood
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics*
  • Adult
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation*
  • Female
  • Folic Acid / blood
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Placenta / metabolism
  • Placenta Diseases / genetics*
  • Placenta Diseases / pathology
  • Pregnancy
  • Premature Birth / genetics*
  • Premature Birth / pathology
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vitamin B 12 / blood

Substances

  • RNA, Messenger
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • MTR protein, human
  • Vitamin B 12