Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India

Mishra, Jyoti; Talwar, Seerat; Kaur, Lovejeet; Chandiok, Ketaki; Yadav, Sneha; Puri, Manju; Sachdeva, M.P.; Ramakrishnan, Lakshmy; Saraswathy, Kallur Nava

doi:10.1016/j.gene.2019.04.036

Cited by 30 publications

(28 citation statements)

References 18 publications

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“…Previous studies have attempted to determine the association between the DNA methylation status and mechanisms that lead to RM. Some studies have suggested that MTHFR is a candidate gene that plays an important role during pregnancy by regulating thrombotic events or methylation (Mishra et al, 2019). Other studies have shown that increasing FOXP3 promoter methylation levels may cause abnormal immune tolerance through downregulation of the expression of FOXP3 protein, which consequently leads to unexplained recurrent spontaneous abortion (Hou et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The relevance of HLA-G and HLA-E expression in the maternal-fetal interface seems to be regarding the inhibition of NK cell-mediated lysis and possible influence on cytokine profiles (Gelmini et al, 2016). Pregnancy is a condition where women undergo major physiological and immunological alterations (Mishra et al, 2019), which are likely to be influenced or controlled by abnormal methylation levels of HLA-G and HLA-E.…”

Section: Discussionmentioning

confidence: 99%

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DNA methylation profiling in recurrent miscarriage

Zhang

et al. 2020

PeerJ

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Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA methylation profiling in recurrent miscarriage

Zhang

et al. 2020

PeerJ

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“…MTHFR genotype-dependent association between lower global DNA methylation and lower plasma folate concentration was detected in observational studies in healthy subjects [81,82,110]. Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia [111]. The combination of MTHFR C677T genotype and diet significantly influenced global DNA methylation in mothers with DS children.…”

Section: Epigenetic Genetic and Nutrigenomic Risk Factors For Congementioning

confidence: 91%

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

Stanković¹

2020

DNA Methylation Mechanism

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During the last decade, quantitative measurement of the methylation status in white blood cells (WBCs) has been used as a potential biomarker in a variety of diseases. Long interspersed nucleotide element-1 (LINE-1) has been used widely as a surrogate marker of global DNA methylation. Altered maternal DNA methylation is suggested to be an underlying mechanism in the trisomy 21 and the development of birth defects, including congenital heart defects (CHDs). The molecular mechanisms that underlie the epigenetic regulation of gene transcription are independent of DNA sequence, but they do depend on environmental stimuli, which are especially important in fetal development in utero environment. Folic acid deficiency and genetic variations of folate pathway genes, such as the methylenetetrahydrofolate reductase gene (MTHFR), are foremost among these maternal risk factors. Also, there are exogenous risk factors (cigarette smoking, alcohol intake, medication use, periconceptional maternal supplementation, body mass index, and dietary habits) with impact on maternal LINE-1 methylation. MTHFR C677T genotype/ diet and other environmental factors as significant predictors of LINE-1 DNA methylation in regard to congenital diseases will be discussed in the chapter.

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“…The relevance of HLA-G and HLA-E expression in the maternal-fetal interface seems to be regarding the inhibition of NK cellmediated lysis and possible influence on cytokine profiles (Gelmini et al 2016). Pregnancy is a condition where women undergo major physiological and immunological alterations (Mishra et al 2019), which are likely to be influenced or controlled by abnormal methylation levels of HLA-G and HLA-E.…”

Section: Mrna Relative Expression Level Of the Candidate Genes In 24 mentioning

confidence: 99%

“…Manuscript to be reviewedDiscussionPrevious studies have attempted to determine the association between the DNA methylation status and mechanisms that lead to RM. Some studies have suggested that MTHFR is a candidate gene that plays an important role during pregnancy by regulating thrombotic events or methylation(Mishra et al 2019). Other studies have shown that increasing FOXP3 promoter methylation levels may cause abnormal immune tolerance through downregulation of the expression of FOXP3…”

mentioning

confidence: 99%

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

2020

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Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RMrelated biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM-receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

show abstract

Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India

Cited by 30 publications

References 18 publications

DNA methylation profiling in recurrent miscarriage

DNA methylation profiling in recurrent miscarriage

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

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