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Purpose: Vitamin D deficiency may be a main causative agent in the pathogenesis of preeclampsia (PE). The actions of the active form of vitamin D are mediated via the vitamin D receptor (VDR), which is expressed in numerous organs including placenta. Therefore, we evaluated the potential relationship between maternal and placental VDR polymorphisms and the predisposition to PE in an Iranian population. Methods: This case–control study surveyed 152 PE and 160 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal and placental VDR Fok1 rs2228570, Bsm1 rs1544410, Taq1 rs731236, and Apa1 rs7975232 polymorphisms. Results: The maternal but not placental VDR FokI Ff genotype, was significantly lower in PE women (P = .02 and P = .06, respectively). The maternal and placental VDR FokI polymorphism was associated with lower PE risk in the dominant model (Ff+ff vs. FF) and these genotypes could decrease PE risk (OR, 0.5 [95% CI, 0.3–0.8], P = .007 and OR, 0.5 [95% CI, 0.3–0.9], P = .02, respectively). The haplotype analysis revealed that the maternal and placental TABf haplotype may lead to decreased risk of PE. In addition, the placental TABF haplotype was associated with higher risk of PE. No relationship was observed between PE susceptibility and the maternal and placental VDR Bsm1, Taq1 and Apa1 polymorphisms. There was also no relationship between the maternal and placental VDR polymorphisms and PE severity. Conclusions: the maternal and placental VDR FokI variant was associated with decreased risk of PE in the dominant model.

MicroRNAs (miRNAs) are a class of noncoding small RNAs which regulate gene expression through post-transcriptional repression or degradation of messenger RNA. They play very important roles in various biological processes including growth, differentiation, and proliferation, as well as apoptosis, angiogenesis, and metabolism. Therefore, in the present study, we evaluated the possible effect of functional rs7372209C/T polymorphism in the 5ˊ- region of pri-miRNA- 26a1gene on preeclampsia(PE) susceptibility. This case-control study was conducted on 219 PE women and 204 unrelated healthy controls. The amplification refractory mutation system-polymerase chain reaction method was used for rs7372209C/T genotyping. The pri-miRNA- 26a1 rs7372209CT genotype was associated with decreased PE risk (OR, 0.5 [95% CI, 0.3–0.8], P = 0.001). The frequency of rs7372209TT genotype did not differ between two groups. In addition, the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of PE in dominant model (CT+TT vs CC) (OR, 0.5 [95% CI, 0.4–0.8], P = 0.002). Although there was no significant difference between mild and severe PE women according to rs7372209CT genotype, the differences between mild and severe PE groups with controls remained significant. The frequency of pri-miRNA-26a1 rs7372209CT genotype was not different between late-onset PE and early onset PE groups. The present study showed for the first time that the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of mild and severe PE in the dominant model and this polymorphism could be a protective factor for PE susceptibility.

Purpose: PE is a pregnancy-specific complication, which genetic and epigenetic factors play key roles in its pathogenesis. DNA methylation is a main epigenetic alteration with important roles in gene regulation. Micro RNAs (miRNAs) as another member of epigenetic machinery regulate the gene expression and involve in different biological pathways including apoptosis and placental development. Therefore, the present study performed to assess the association between miRNA-34a promoter methylation and PE susceptibility. Methods: The placenta of 104 PE pregnant women and 119 normotensive pregnant women were collected after delivery. The methylation status of the miRNA-34a promoter was assessed using Methylation Specific PCR (MSP). Results: The frequency of the hemi-methylated (MU) miR-34a promoter was significantly lower in PE women compared to the controls (17.3 vs. 29.4%) (OR, 0.45 [95% CI, 0.2–0.9], P = 0.016). The overall methylation rate was 23.1% in PE women and 41.2% in the control group and was significantly lower in PE women (OR, 0.4 [95% CI, 0.2–0.8], P = 0.004). The frequency of hemi-methylated (MU) and overall methylated (MU+MM) promoter of miR-34a gene was significantly lower in severe PE but not in mild PE women compared to the controls [(OR, 0.3 [95% CI, 0.1–0.8], P = 0.02) and (OR, 0.3 [95% CI, 0.1–0.7], P = 0.009), respectively]. There was an association between hemi-methylated (MU) and overall methylated (MU+MM) promoter and late onset PE [(OR, 0.4 [95% CI, 0.2–0.9], P = 0.03) and (OR, 0.4 [95% CI, 0.2–0.8], P = 0.01), respectively]. Conclusions: An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.

Purpose: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Methods: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. Results: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1–2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4–6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC–GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4–8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 – 2], P = 0.01). Conclusions: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC–GG combined genotype and C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.