Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India

Gene. 2019 Jul 1;704:68-73. doi: 10.1016/j.gene.2019.04.036. Epub 2019 Apr 12.

Abstract

Aim: The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism.

Methods: The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP.

Results higher: Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts.

Conclusion: The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.

Keywords: DNA methylation; Global methylation; MTHFR gene specific methylation; Preeclampsia; Pregnancy complications; Recurrent miscarriages.

MeSH terms

  • Abortion, Habitual / genetics*
  • Adult
  • Case-Control Studies
  • DNA Methylation*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Homocystinuria / complications
  • Homocystinuria / genetics
  • Humans
  • India
  • Methylenetetrahydrofolate Reductase (NADPH2) / deficiency
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Muscle Spasticity / complications
  • Muscle Spasticity / genetics
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Pregnancy Trimester, Second / genetics
  • Pregnancy Trimester, Third / genetics
  • Psychotic Disorders / complications
  • Psychotic Disorders / genetics

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Supplementary concepts

  • Methylenetetrahydrofolate reductase deficiency