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

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 ObjectivesThis 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 (χ 2 = 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.

Susceptibility to hypertension based on MTHFR rs1801133 single nucleotide polymorphism and MTHFR promoter methylation

“…Our results support the view that DNA methylation might be involved in the association between the MTHFR gene and hypertension. MTHFR hypomethylation was associated with lower levels of MTHFR and higher levels of homocysteine ( 82 , 86 ). MTHFR promoter hypermethylation was protective against ischemic stroke, implying that it could be a diagnostic marker for the disease ( 86 ).…”

“…The mechanism behind the link between MTHFR rs1801133 and hypertension is unclear. Epigenetic changes in the regulatory region, especially MTHFR promoter methylation levels are believed to affect gene expression, regardless of genetic mutations ( 82 ). Moreover, DNA methylation and epigenetic pathways are reversible and believed to be potential preventive and therapeutic targets in hypertension management ( 15 ).…”