DNA repair is reduced in patients suffering from systemic lupus erythematosus (SLE), and it can induce the production of autoreactive antibodies due to the accumulation of DNA damage and nucleoprotein that produce immunogenic antigens. The accumulations of anti-Ku and DNA-PKcs antibodies, which are involved in nonhomologous DNA end joining pathway, have been detected in SLE patients. The present study was designed to evaluate the association of XRCC5, XRCC6, and XRCC7 polymorphisms with SLE susceptibility. Polymerase chain reaction (PCR) was performed to genotype 163 SLE patients and 180 healthy controls for the XRCC5 variable number of tandem repeat (VNTR) polymorphism. The genotype analysis of XRCC6-61C>G and XRCC7 6721G>T polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was a significant association between XRCC5 VNTR, XRCC7 6721G>T polymorphisms and risk of SLE development. Notably, the frequency of XRCC5 VNTR 0R allele and genotypes with 2R allele was greatly enhanced in SLE patients with Malar rash (p=0.032 and p=0.024, respectively). Moreover, a higher frequency of genotypes with the XRCC5 VNTR 2R allele was observed in SLE patients with a positive antinuclear antibody (ANA) test (p=0.03). The present study shows an association between the XRCC5 VNTR, XRCC7 6721G>T polymorphisms and SLE. These polymorphisms might be genetic risk factors for SLE susceptibility and some SLE manifestations in the population southeast of Iran.

Preeclampsia (PE) is a pregnancy-specific complication which is a major cause of maternal and fetal morbidity and mortality. Recent studies have shown the aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE. Dicer1 is a key enzyme in the generation of small noncoding RNAs including miRNAs. The aim of this study is to investigate the relationship between maternal and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression in PE and normotensive pregnant women. The blood and placenta of PE pregnant and normotensive pregnant women were collected after delivery. Dicer1 rs3742330 polymorphism was genotyped using PCR-RFLP method. The mRNA expression levels were measured using quantitative real time PCR. The maternal Dicer1 rs3742330 polymorphism was not associated with PE or PE severity; however, the placental Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The relative mRNA expression of Dicer1 gene in the placenta did not differ between the two groups. In addition, the relative mRNA expression of Dicer1 gene was significantly lower in the placenta of women with rs3742330 AG+GG genotypes in the total population (P = 0.028) and PE women (P = 0.004), but not in the control group. In conclusion, there was a relationship between placental but not maternal Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA expression between the PE and control groups; however, it was significantly lower in the placenta of women with rs3742330 AG+GG genotypes.

Preeclampsia (PE) is a pregnancy specific complication arises in presence of the placenta and disappears immediately after delivery. Therefore, the aim of the present study was to investigate the possible effects of the placental 3'-UTR rs1537514C>G and rs4846049C>A polymorphisms and DNA methylation of the MTHFR gene on the MTHFR mRNA expression. The placenta of 74 PE pregnant women and 75 normotensive pregnant women were collected after delivery. The methylation status of the MTHFR promoter was assessed with Methylation Specific PCR (MSP). The rs1537514C>G and rs4846049C>A polymorphisms were genotyped using PCR-RFLP method. The mRNA expression levels were measured by Quantitative Real Time PCR. The results showed the lower MTHFR mRNA expression in the placenta of PE women. There was an association between hypermethylation and lower MTHFR mRNA expression in PE women and entire women but not normotensive pregnant women. The frequency of MTHFR rs1537514CG genotype was significantly lower in PE women; however, there was no association between MTHFR rs4846049C>A polymorphism and PE. The combination effects of MTHFR CG/AC genotypes and G-A haplotype of MTHFR rs1537514/rs4846049 polymorphisms were associated with lower risk of PE. The MTHFR rs1537514G (4869G) allele was associated with higher MTHFR mRNA expression in both groups. However, there was no relation between MTHFR rs4846049C>A polymorphism and MTHFR mRNA expression. Our findings showed lower MTHFR mRNA expression in PE women. The MTHFR rs1537514C>G polymorphism was associated with lower PE risk and MTHFR mRNA expression. Lower expression of MTHFR mRNA was observed in the women with the hypermethylated promoter.

The current study found higher mRNA expression of placental VEGF gene in PE women. The mRNA expression of the placental VEGF gene has been up-regulated in the placenta of women with -634CC genotype. No association was found between the placental VEGF -1154G/A and -2549 I/D polymorphisms and VEGF mRNA expression.

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