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Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre-eclampsia

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Abstract

Background

Genetic and epigenetic factors play significant roles in the aetio-pathogenesis of pre-eclampsia (PE). The effects may vary across racial and geographical boundaries. The role of epigenetic modification in pre-eclampsia was studied among African populations in Lagos, Nigeria.

Aim and Objectives

This study aimed to determine the pattern of Methylene tetrahydrofolate reductase gene (MTHFR) CpG island methylation in pre-eclampsia, and evaluate associated covariates.

Methodology

This study was an observational, cross-sectional, study conducted at the Lagos University Teaching Hospital and the Lagos State Island Maternity Hospital. A total of 400 pregnant women consisting of 200 pregnant women diagnosed with pre-eclampsia (study group) and 200 pregnant normotensive and apparently healthy women (control group) were recruited for the study. Demographic and clinical histories were obtained through questionnaires. The DNA Methylation status of the CpG Island in promoter region of the MTHFR gene was assessed using bisulphite conversion and methylation specific PCR method. The biochemical parameters measured in the study were: red cell folate, vitamin B12, plasma homocysteine (Hcy) and methylene tetrahydrofolate reductase enzyme level.

Results

Homozygous MTHFR CpG island hypomethylation pattern was significantly associated with pre-eclampsia (χ2 = 22.96; p = 0.000), Mean values of plasma homocysteine in PE women with homozygous hypomethylation (26.1 ± 9.1 umol/L) were significantly higher than (20.1 ± 4.2 umol/L) observed in PE subjects with homozygous hypermethylation (p = 0.008). Homozygous CpG island hypomethylated pattern of the MTHFR promoter region, was associated with the lowest median MTHFR enzyme level (72.8 ± 39.8 pmol/L) compared with heterozygous methylated pattern (91.3 ± 60.9 pmol/L; p = 0.047) and homozygous methylated pattern (82.3 ± 31.0 pmol/L; 0.047). Red cell folate and Vitamin B12 levels were not significantly associated with CpG island methylation status.

Conclusion

Epigenetic modification plays significant role in the pathogenesis of pre-eclampsia.

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Authors and Affiliations

  1. Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria

    V. O. Osunkalu & A. A. Abiola

  2. Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria

    I. A. Taiwo

  3. Department of Cell Biology and Genetics, University of Lagos, Lagos, Nigeria

    C. C. Makwe & R. I. Anorlu

  4. Department of Community Health and Primary Care, Lagos, Nigeria

    R. A. Quao

Authors
  1. V. O. Osunkalu
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  2. I. A. Taiwo
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  3. C. C. Makwe
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  4. A. A. Abiola
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  5. R. A. Quao
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  6. R. I. Anorlu
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Contributions

Osunkalu Vincent: Conceptualization, data analysis and manuscript writing. Idowu Taiwo: Conceptualization, Genetic analysis and study design, literature review. Makwe Christain: Article review, literature review, project supervision. Abiola Ann Ogbenna: Article review, literature review, project supervision Quao Rachel: statistical analysis and editing. Anorlu Rose: Article review, literature review, project supervision.

Corresponding author

Correspondence to V. O. Osunkalu.

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Conflict of interest

All authors declare no conflict of interest whatsoever.

Human and Animal Rights

Research involving Human participants only. The study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helenski and its amendments or comparable ethical standards.

Informed Consent

Study was approved by the Human Research and Ethical Committee of the Lagos University Teaching Hospital, Nigeria. Written and oral informed consent were obtained from all participants before recruitment into the study.

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Osunkalu, Vincent Oluseye is an Associate Professor of Haematology and Blood Transfusion at the College of Medicine of the University of Lagos, Lagos, Nigeria. Idowu Taiwo, is an Associate Professor of Cell Biology and Genetics from the University of Lagos, Lagos, Nigeria. Makwe Christian is a Senior Lecturer in the Department of Obstetrics and Gynaecology at the University of Lagos, Lagos, Nigeria. Anorlu Rose is a Professor from the Department of Obstetrics and Gynaecology at the College of Medicine, University of Lagos, Lagos, Nigeria. Quao Rachel Abiana is a Graduate from the Physiology Department at the College of Medicine, University of Lagos, Lagos, Nigeria.

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Osunkalu, V.O., Taiwo, I.A., Makwe, C.C. et al. Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre-eclampsia. J Obstet Gynecol India 71, 52–57 (2021). https://doi.org/10.1007/s13224-020-01374-w

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  • DOI: https://doi.org/10.1007/s13224-020-01374-w

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