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

摘要

Background Genetic and epigenetic factors play signifcant roles in the aetio-pathogenesis of pre-eclampsia (PE). The efects may vary across racial and geographical boundaries. The role of epigenetic modifcation 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 specifc 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 signifcantly 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 signifcantly associated with CpG island methylation status. Conclusion Epigenetic modifcation plays signifcant role in the pathogenesis of pre-eclampsia.