Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia

Mohammadpour‐Gharehbagh, Abbas; Jahantigh, Danial; Eskandari, Moein; Harati‐Sadegh, Mahdiyeh; Nematollahi, Mohammad Hadi; Rezaei, Mahnaz; Rasouli, Ava; Eskandari, Fatemeh; Heydarabad, Milad Zadi; Teimoori, Batool; Salimi, Saeedeh

doi:10.1007/s10495-018-1501-8

Cited by 28 publications

(14 citation statements)

References 52 publications

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“…Although numerous reports have been made on the association between maternal and fetal gene polymorphisms and PE, there is no report on the association between placental/fetal H19 polymorphisms and PE based on our review. Nevertheless, the relationship between H19 polymorphisms and several diseases, including coronary artery disease, molar tissues, and cancers has been reported.…”

Section: Discussionmentioning

confidence: 80%

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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The effect of DNA methylation on gene expression triggered it as a susceptibility factor in various diseases including preeclampsia (PE). The pathogenesis of PE is closely associated with the methylation status and genetic variants of relevant genes. Therefore, the aim of the study was to investigate the possible impacts of the placental DNA methylation and rs3741219, rs217727, and rs2107425 polymorphisms of the H19 gene on the PE susceptibility as well as the its mRNA expression. Moreover, eight haplotypes of three loci in the H19 gene were analyzed. In this case‐control study, the placentas of 107 preeclamptic and 113 non‐preeclamptic women were collected after delivery. The methylation status was assessed by methylation‐specific polymerase chain reaction (PCR). The H19 polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism or amplification refractory mutation system‐polymerase chain reaction methods. The quantitative real time PCR was used for mRNA expression assay. The placental H19 rs3741219 and rs2107425 polymorphisms were not associated with PE. However, H19 rs217727CT and TT genotypes might be associated with a 9.2‐ and 17.7‐fold increased risk of PE, respectively. The Trs3741219 Crs217727 Crs2107425 and Trs3741219 Crs217727 Trs2107425 haplotypes were significantly lower, whereas the Trs3741219 Trs217727 Crs2107425 and Crs3741219 Trs217727 Crs2107425 haplotypes were significantly higher in PE women. Promoter but not upstream region hypermethylation of H19 gene could be led to decreased risk of PE (MM vs. UM + UU). No significant difference was observed in the placental mRNA expression between two groups. The H19 expression was significantly higher in women with unmethylated (UU), compared to methylated promoter (MM). The H19 expression was 17‐ and 15‐fold higher in H19‐rs2107425 CC and CT genotypes in PE women. In conclusion, the H19 rs2107425 polymorphism was associated with a higher risk of PE and increased H19 mRNA expression. The promoter hypermethylation of H19 gene was associated with a lower risk of PE and decreased H19 mRNA expression.

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Section: Discussionmentioning

confidence: 80%

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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“…In recent years, epigenetic regulation of placental gene expression has been considered to play an important role in human trophoblast differentiation (Gamage et al, 2018) and contribute to the onset of PE (Chelbi and Vaiman, 2008;Leavey et al, 2018). The studies showed higher expression levels of death domain-associated protein 6 (DAXX), MMP9, and BCL2 in placenta from PE tissue, and this increased expression was well correlated to promoter demethylation (Wang et al, 2010;Novakovic et al, 2017;Mohammadpour-Gharehbagh et al, 2019). However, a significant number of the observed methylation changes were not associated with corresponding changes in gene expression, and vice versa (Gamage et al, 2018;Leavey et al, 2018), indicating that alternate methods of epigenetic regulation will need to be explored in PE.…”

Section: Discussionmentioning

confidence: 99%

H3K4me3-Mediated Upregulation of LncRNA-HEIPP in Preeclampsia Placenta Affects Invasion of Trophoblast Cells

Sun

Huaiyan

et al. 2020

Front. Genet.

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Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway–related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the lncRNA-HEIPP promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)–quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on lncRNA-HEIPP promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.

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“…Previous studies were proved the role of plenty of individual genetic variants in susceptibility to human carcinomas and complex disorders . A large number of studies have been carried out on candidate genes to illustrate the role of genetics in PTC development, but the findings show no similar results for a gene .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies were proved the role of plenty of individual genetic variants in susceptibility to human carcinomas and complex disorders. 21,22 A large number of studies have been carried out on candidate genes to illustrate the role of genetics in PTC development, but the findings show no similar results for a gene. 23,24 Despite the powerful effect of oxidative stress mechanisms on cancer susceptibility including PTC, a few gene variants have been investigated and inconsistent results have also been reported.…”

Section: Discussionmentioning

confidence: 99%

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma

et al. 2020

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Several lines of evidences have indicated that inflammation play an important role in the carcinogenesis. During the inflammatory processes, free radical species are produced from oxidative stress. In normal conditions, enzymatic and nonenzymatic antioxidants remove these products. Manganese superoxide dismutase (MnSOD), glutathione peroxidase‐1 (GPx‐1), and catalase (CAT) are three important enzymes. Therefore, this study aimed to evaluate the effects of MnSOD (SOD2), GPX‐1, and CAT genetic polymorphisms on papillary thyroid carcinoma (PTC) susceptibility. A total of 134 patients with PTC and 151 healthy controls were recruited to participate in this study. All samples were genotyped for SOD2 rs4880, GPX1 1050450, and CAT rs7943316 polymorphisms by polymerase chain reaction‐restriction fragment length polymorphism method. The frequencies of the rs1050450, rs4880, and rs7943316 alleles and genotypes were not different between PTC patients and controls. However, the TC genotype of SOD2 rs4880 polymorphism was significantly higher in males compared to that in females in PTC patients (odds ratio [OR], 3.9 [95% CI, 1.5–11], p = .007). The rs4880 polymorphism was also associated with higher stages (III‐IV) of PTC in dominant model. No significant correlation was found between GPX1‐rs1050450 and CAT‐rs7943316 polymorphisms and demographic, clinical, and pathological features of the disease. The SOD2 rs4880CT genotype was more frequent in males with PTC and patients with higher stages (III–IV) of disease (OR, 2.9 [95% CI, 1.1–7.7], p = .04). However, no significant association was found between GPX1‐rs1050450 and CAT‐rs7943316 variants and PTC or its demographic, clinical, and pathological features.

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Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia

Cited by 28 publications

References 52 publications

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

H3K4me3-Mediated Upregulation of LncRNA-HEIPP in Preeclampsia Placenta Affects Invasion of Trophoblast Cells

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma

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