Altered methylation and expression patterns of genes regulating placental nitric oxide pathway in patients with severe preeclampsia

Azizi, Faezeh; Omrani, Mir Davood; Amiri, Vahid; Mirfakhraie, Reza; Dodangeh, Fatemeh; Shahmirzadi, Sedigheh Asadi; Gargari, Soraya Saleh

doi:10.3233/hab-180356

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…In previous epigenetic research, pre-eclampsia is the most extensively studied of the pregnancy complications, although more often methylation of the placenta rather than blood. A few studies have targeted specific hypotheses: pre-eclampsia has been associated with hypermethylation of HLA-G promoter (chromosome 6p22.1) [ 48 ], hypomethylation of the CTGF promoter, differential methylation of the genes regulating placental nitric oxide (DDAH2) [ 49 ], and hypermethylation of 5,10-MTHFR [ 50 ]. Although none of these were clearly differentially methylated in this analysis, one site in the MTHFR gene was nominally associated with history of pre-eclampsia (beta 0.0078, SD 0.002, p = 0.0003).…”

Section: Discussionmentioning

confidence: 99%

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

et al. 2021

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Background Women with a history of complications of pregnancy, including hypertensive disorders, gestational diabetes or an infant fetal growth restriction or preterm birth, are at higher risk for cardiovascular disease later in life. We aimed to examine differences in maternal DNA methylation following pregnancy complications. Methods Data on women participating in the Young Finns study (n = 836) were linked to the national birth registry. DNA methylation in whole blood was assessed using the Infinium Methylation EPIC BeadChip. Epigenome-wide analysis was conducted on differential CpG methylation at 850 K sites. Reproductive history was also modeled as a predictor of four epigenetic age indices. Results Fourteen significant differentially methylated sites were found associated with both history of pre-eclampsia and overall hypertensive disorders of pregnancy. No associations were found between reproductive history and any epigenetic age acceleration measure. Conclusions Differences in epigenetic methylation profiles could represent pre-existing risk factors, or changes that occurred as a result of experiencing these complications.

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Section: Discussionmentioning

confidence: 99%

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

et al. 2021

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Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity

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Tirozzi

et al. 2021

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Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several pathological conditions especially in cancer, cardiovascular, autoimmune and inflammatory diseases. Little is known about the genetics of circulating PlGF levels. Indeed, although the heritability of circulating PlGF levels is around 40%, no studies have assessed the relation between PlGF plasma levels and genetic variants at a genome-wide level. In the current study, PlGF plasma levels were measured in a population-based sample of 2085 adult individuals from three isolated populations of South Italy. A GWAS was performed in a discovery cohort (N = 1600), followed by a de novo replication (N = 468) from the same populations. The meta-analysis of the discovery and replication samples revealed one signal significantly associated with PlGF circulating levels. This signal was mapped to the PlGF co-receptor coding gene NRP1, indicating its important role in modulating the PlGF plasma levels. Two additional signals, at the PlGF receptor coding gene FLT1 and RAPGEF5 gene, were identified at a suggestive level. Pathway and TWAS analyses highlighted genes known to be involved in angiogenesis and immune response, supporting the link between these processes and PlGF regulation. Overall, these data improve our understanding of the genetic variation underlying circulating PlGF levels. This in turn could lead to new preventive and therapeutic strategies for a wide variety of PlGF-related pathologies.

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Altered methylation and expression patterns of genes regulating placental nitric oxide pathway in patients with severe preeclampsia

Cited by 2 publications

References 24 publications

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity

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