Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre‑eclampsia
Date
2020
Authors
Osunkalu, V.O
Taiwo, I.A
Makwe, C.C
Ogbenna, A.A
Quao, R.A
Anorlu, R.I
Journal Title
Journal ISSN
Volume Title
Publisher
The Journal of Obstetrics and Gynecology of India
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.
Description
Keywords
Epigenetics , Methylation , Pre-eclampsia , Homocysteine , Methylene tetrahydrofolate reductase
Citation
Osunkalu, V.O., Taiwo, I.A., Makwe, C.C., Ogbenna, A.A., Quao, R.A. and Anorlu, R.I. (2020). Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre‑eclampsia. The Journal of Obstetrics and Gynecology of India, 71,52-57.