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

Abstract

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.

H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study

“…The genotype-speci c methylation changes at the H19 ICR in assisted reproductive technology derived placentas is associated with the polymorphism rs10732516 [40]. It has also been reported hypomethylation status in promoter region of H19 gene indicated a higher risk of preeclampsia, H19 mRNA expression was higher in recessive model , but there was no association between mRNA expression and placental H19 associated polymorphisms [35]. This may suggest that the effect of H19 risk SNPs on DNA methylation in Wilms tumor.…”

“…The genetic changes that underpin Wilms tumor are diverse, many studies have de ned cancer genes that harbor likely driver mutations [34]. H19 is found in an imprinted region of chromosome 11, contains ve exons and four small introns, and the three SNPs rs2839698, rs3024270 and rs217727 located in exon 1, intron and exon 5, respectively [35]. DNA methylation in uences gene expression and protein levels through epigenetic modi cation, thereby promoting the development of various diseases [36].…”

H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study

“…The genetic changes that underpin Wilms tumor are diverse, many studies have defined cancer genes that harbor likely driver mutations (Treger et al, 2019). H19 is found in an imprinted region of chromosome 11, contains five exons and four small introns, and the three SNPs we studied rs2839698, rs217727, and rs3024270 located in exon 1, exon 5, and intron, respectively (Harati‐Sadegh et al, 2020). DNA methylation influences gene expression and protein levels through epigenetic modification, thereby promoting the development of various diseases (Okamoto et al, 1997).…”

The Role of Long Non-Coding RNAs in Trophoblast Regulation in Preeclampsia and Intrauterine Growth Restriction

“…They showed 32 differentially expressed lncRNAs, including the expression of H19, which was significantly downregulated in term placentae of early-onset severe PE patients [ 116 ]. Furthermore, H19 rs2107425 polymorphism was associated with a higher risk of PE; on the other hand, the placental promoter hypermethylation of the H19 gene was associated with a lower risk of PE [ 117 ].…”