The effect of the placental DROSHA rs10719 and rs6877842 polymorphisms on PE susceptibility and mRNA expression
Mahnaz Rezaei1, Abbas Mohammadpour-Gharehbagh1,2, Mehrnaz Narooei-Nejad3
1Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Abstract:
Evidence showed that microRNA biosynthesis plays the main role in pathogenesis of several diseases including Preeclampsia (PE). Therefore, microRNA processing enzymes may involve in PE predisposition. The aim of the present study was to evaluate the relation between DROSHA rs10719 and rs6877842 polymorphisms and mRNA expression in the placenta of PE women and controls. This study recruited 110 PE women and 115 age matched normotensive pregnant women for genotyping of DROSHA polymorphisms and analyzing of mRNA expression. There was no association between alleles and genotypes of placental DROSHA rs10719 and rs6877842 polymorphisms and PE susceptibility. However, placental DROSHA rs10719 was associated with increased PE risk in the recessive model. The combination of CC/GG genotypes of DROSHA rs10719 and rs6877842 polymorphisms was associated with higher risk of PE. The frequency of C-G haplotype was higher in PE women, but the difference was not significant. The DROSHA mRNA expression was downregulated in the placenta of PE women. There was no relation between DROSHA mRNA expression and rs6877842 polymorphism, however, it was decreased in the placenta of women with rs10719CC genotype. The placental DROSHA rs10719 but not rs6877842 polymorphism could be a risk factor for PE susceptibility only in the recessive model. The combination of CC/GG genotypes could be risk factors for PE susceptibility. The DROSHA expression downregulated in the preeclamptic placentas and those carrying rs10719CC genotype.
Insights
Preeclampsia (PE) risk may be linked to the DROSHA rs10719 gene variant, particularly in a recessive model. DROSHA mRNA expression was lower in placentas from PE patients, especially those with the rs10719CC genotype.
Area of Science:
- Genetics
- Obstetrics
- Molecular Biology
Background:
- MicroRNA biosynthesis is implicated in Preeclampsia (PE) pathogenesis.
- MicroRNA processing enzymes, like DROSHA, may influence PE predisposition.
Purpose of the Study:
- To investigate the association between DROSHA gene polymorphisms (rs10719 and rs6877842) and mRNA expression in the placenta of PE patients and controls.
- To evaluate the role of DROSHA variants in PE susceptibility.
Main Methods:
- Genotyping of DROSHA rs10719 and rs6877842 polymorphisms in 110 PE women and 115 controls.
- Analysis of DROSHA mRNA expression in placental tissues.
- Statistical analysis to assess associations between genotypes, haplotypes, mRNA levels, and PE risk.
Main Results:
- No overall association between DROSHA rs10719/rs6877842 alleles/genotypes and PE susceptibility.
- DROSHA rs10719 was associated with increased PE risk in a recessive model.
- Combined CC/GG genotypes of rs10719 and rs6877842 were linked to higher PE risk.
- DROSHA mRNA expression was downregulated in PE placentas.
- Decreased DROSHA mRNA expression was observed in placentas with the rs10719CC genotype.
Conclusions:
- The placental DROSHA rs10719 polymorphism, specifically in the recessive model, may be a risk factor for PE susceptibility.
- Combined genotypes (CC/GG) of DROSHA rs10719 and rs6877842 could increase PE risk.
- Downregulation of DROSHA expression in preeclamptic placentas, particularly in carriers of the rs10719CC genotype, warrants further investigation.
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