Association of methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes promoter methylation pattern with the risk of essential hypertension

IF 0.8 Q4 GENETICS & HEREDITY Meta Gene Pub Date : 2021-09-01 DOI:10.1016/j.mgene.2021.100914

Shabnaz Koochakkhani , Fatemeh Nabizadeh , Azim Nejatizadeh , Ebrahim Eftekhar

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Abstract

Methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) are key enzymes in the metabolism of homocysteine pathway whose dysfunction can lead to essential hypertension (EH). This study aimed to investigate the possible association of MTHFR and CBS genes promoter methylation patterns with the risk of EH. We also aimed to search differentially expressed microRNAs (miRs) and demonstrate the role of miRs in the aberrant DNA methylation in essential hypertensive patients by targeting DNA methyltransferases (DNMTs).

20 essential hypertensive patients and 20 healthy controls were selected. DNA methylation levels of 10 CpG dinucleotides on MTHFR and 19 CpG dinucleotides on CBS genes promoter was measured using Bisulfite-Sequencing PCR (BSP). The GSE118578 profile was downloaded from the GEO database to identify differentially expressed miRs in hypertensive patients and R statistical software was used to analyze the data. Enrichment analysis was conducted to predict target genes using databases of Targetscan, and miRDB-MicroRNA Target Prediction Database.

No significant association between MTHFR gene methylation and EH was observed. There was a significant association between one of the CpG sites of CBS gene promoter (CpG19 (+1035C)) and EH [OR = 5.3(0.895–31.393), p = 0.047]. Furthermore, we reported a list of miRs that may have an essential role in regulating DNA methylation by targeting DNMTs.

Our findings showed that hypermethylation of CpG19 (+1035C) of CBS gene promoter could increase the risk of EH. Methylation status of MTHFR gene had no significant association with EH. Also, in-silico investigation showed that miRs may affect aberrant genes methylation through altering DNMTs biogenesis.

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亚甲基四氢叶酸还原酶(MTHFR)和胱硫氨酸β合酶(CBS)基因启动子甲基化模式与原发性高血压风险的关联

亚甲基四氢叶酸还原酶(MTHFR)和胱硫氨酸β合酶(CBS)是同型半胱氨酸通路代谢的关键酶，其功能障碍可导致原发性高血压(EH)。本研究旨在探讨MTHFR和CBS基因启动子甲基化模式与EH风险的可能关联。我们还旨在寻找差异表达的microRNAs (miRs)，并通过靶向DNA甲基转移酶(dnmt)来证明miRs在原发性高血压患者异常DNA甲基化中的作用。选取原发性高血压患者20例，健康对照20例。采用亚硫酸盐测序PCR (bisulte - sequencing PCR, BSP)检测了MTHFR上10个CpG二核苷酸和CBS基因启动子上19个CpG二核苷酸的DNA甲基化水平。从GEO数据库下载GSE118578基因图谱，识别高血压患者差异表达的miRs，并使用R统计软件对数据进行分析。利用Targetscan和miRDB-MicroRNA靶基因预测数据库进行富集分析预测靶基因。MTHFR基因甲基化与EH无显著相关性。CBS基因启动子CpG位点之一CpG19 (+1035C)与EH有显著相关性[OR = 5.3(0.895-31.393)， p = 0.047]。此外，我们报道了一系列miRs，这些miRs可能通过靶向dnmt在调节DNA甲基化中发挥重要作用。结果表明，CBS基因启动子CpG19 (+1035C)的高甲基化可增加EH的风险。MTHFR基因甲基化状态与EH无显著相关性。此外，计算机研究表明，miRs可能通过改变dnmt的生物发生来影响异常基因的甲基化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Meta Gene Biochemistry, Genetics and Molecular Biology-Genetics

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1.10

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0.00%

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期刊介绍： Meta Gene publishes meta-analysis, polymorphism and population study papers that are relevant to both human and non-human species. Examples include but are not limited to: (Relevant to human specimens): 1Meta-Analysis Papers - statistical reviews of the published literature of human genetic variation (typically linked to medical conditionals and/or congenital diseases) 2Genome Wide Association Studies (GWAS) - examination of large patient cohorts to identify common genetic factors that influence health and disease 3Human Genetics Papers - original studies describing new data on genetic variation in smaller patient populations 4Genetic Case Reports - short communications describing novel and in formative genetic mutations or chromosomal aberrations (e.g., probands) in very small demographic groups (e.g., family or unique ethnic group). (Relevant to non-human specimens): 1Small Genome Papers - Analysis of genetic variation in organelle genomes (e.g., mitochondrial DNA) 2Microbiota Papers - Analysis of microbiological variation through analysis of DNA sequencing in different biological environments 3Ecological Diversity Papers - Geographical distribution of genetic diversity of zoological or botanical species.