子痫前期女性亚甲基四氢叶酸还原酶（MTHFR）基因的表观遗传修饰

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

作者信息

Osunkalu V O, Taiwo I A, Makwe C C, Abiola A A, Quao R A, Anorlu R I

机构信息

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

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

出版信息

J Obstet Gynaecol India. 2021 Feb;71(1):52-57. doi: 10.1007/s13224-020-01374-w. Epub 2020 Sep 30.

DOI:10.1007/s13224-020-01374-w

PMID:33814799

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7960825/

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 ( = 22.96; = 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 ( = 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; = 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.

摘要

背景

遗传和表观遗传因素在子痫前期（PE）的病因发病机制中起重要作用。这些影响可能因种族和地域的不同而有所差异。在尼日利亚拉各斯的非洲人群中研究了表观遗传修饰在子痫前期中的作用。

目的

本研究旨在确定子痫前期中亚甲基四氢叶酸还原酶基因（MTHFR）CpG岛甲基化模式，并评估相关协变量。

方法

本研究是在拉各斯大学教学医院和拉各斯州岛妇产医院进行的一项观察性横断面研究。共招募了400名孕妇，其中包括200名被诊断为子痫前期的孕妇（研究组）和200名血压正常且明显健康的孕妇（对照组）。通过问卷调查获取人口统计学和临床病史。使用亚硫酸氢盐转化和甲基化特异性PCR方法评估MTHFR基因启动子区域CpG岛的DNA甲基化状态。本研究中测量的生化参数包括：红细胞叶酸、维生素B12、血浆同型半胱氨酸（Hcy）和亚甲基四氢叶酸还原酶水平。

结果

MTHFR CpG岛纯合子低甲基化模式与子痫前期显著相关（χ² = 22.96；P = 0.000），纯合子低甲基化的子痫前期女性血浆同型半胱氨酸的平均值（26.1±9.1μmol/L）显著高于纯合子高甲基化的子痫前期患者（20.1±4.2μmol/L）（P = 0.008）。与杂合子甲基化模式（91.3±60.9pmol/L；P = 0.047）和纯合子甲基化模式（82.3±31.0pmol/L；P = 0.047）相比，MTHFR启动子区域的纯合子CpG岛低甲基化模式与最低的MTHFR酶水平中位数（72.8±39.8pmol/L）相关。红细胞叶酸和维生素B12水平与CpG岛甲基化状态无显著关联。