Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre-eclampsia
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ORIGINAL ARTICLE
Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre‑eclampsia V. O. Osunkalu1 · I. A. Taiwo2 · C. C. Makwe3 · A. A. Abiola1 · R. A. Quao4 · R. I. Anorlu3 Received: 19 February 2020 / Accepted: 2 September 2020 © Federation of Obstetric & Gynecological Societies of India 2020
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. Keywords Epigenetics · Methylation · Pre-eclampsia · Homocysteine · Methylene tetrahydrofolate reductase
Introduction 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 C
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