The −2549 insertion/deletion polymorphism of VEGF gene associated with uterine leiomyoma susceptibility in women from Southeastern Iran

Objectives: Vascular endothelial growth factor (VEGF) is an important angiogenic factor that regulates angiogenesis and mediates sex steroid-induced cell growth. The present study investigated the association of VEGF gene-2578C/A (rs699947) and −2549 insertion/deletion polymorphisms in the promoter region of VEGF-A gene and uterine leiomyoma susceptibility in Southeast of Iran. Material and methods: One hundred and fifty five women with uterine leiomyoma and 157 age, BMI, and ethnicity matched healthy women were enrolled in this study. VEGF gene –2578C/A polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the –2549 insertion/dele­tion polymorphism was analyzed by PCR method. Results: The frequency of alleles and genotypes of VEGF-2578C/A polymorphism was not different between women with uterine leiomyoma and the controls; however, a significant association was revealed between II genotype of –2549 insertion/deletion (I/D) polymorphism of VEGF gene and uterine leiomyoma. Conclusions: The findings showed that VEGF gene –2549 insertion/deletion polymorphism was associated with uterine leiomyoma

The Efficacy of Zinc Administration in the Treatment of Primary Dysmenorrhea

Objectives: Dysmenorrhea is a common complaint in women. Primary dysmenorrhea is defined as painful menstruation in the absence of pelvic disease and is caused by uterine contractions caused by prostaglandins released from the endometrium. Conventional treatments include nonsteroidal anti-inflammatory drugs and oral contraceptives. We sought to evaluate the efficacy of zinc supplementation in the treatment of primary dysmenorrhea.  Methods: Two-hundred participants with primary dysmenorrhea were randomized into one of two groups. The intervention group received zinc and mefenamic acid, and the control group received mefenamic acid and a placebo drug. After three months of treatment, changes in the incidence of dysmenorrhea and the degree of pain were measured in both groups.  Results: The mean pain score before administration of zinc and mefenamic acid in the intervention group was 5.3±1.8 and after treatment was 1.2±1.9 (p 0.050). We also found that 64% of case group and 33% of the control group did not experience dysmenorrhea after treatment (p < 0.001).  Conclusions: The use of a zinc supplement in combination with mefenamic acid was superior in reducing primary dysmenorrhea compared to mefenamic acid alone

Conjoined twins in a monochorionic triplet pregnancy after in vitro fertilization: a case report

Background: Monozygotic monochorionic triplet pregnancy with conjoined twins is a very rare condition and is associated with many complications. Case: In this study, we describe a monochorionic–diamniotic triplet pregnancy after in vitro fertilization with an intracytoplasmic sperm injection. At a gestational age of 6 weeks and 4 days of pregnancy one gestational sac was observed, and at a gestational age of 12 weeks and 2 days, triplets with conjoined twins were diagnosed. After consulting with the parents, they chose fetal reduction of the conjoined twins. Selective feticide was successfully performed by radiofrequency ablation at 16 weeks of pregnancy. Unfortunately, the day after the procedure, the membrane ruptured, and 1 week later, all fetuses and placenta were spontaneously aborted. Conclusion: Monochorionic triplet pregnancy with conjoined twins is very rare. These pregnancies are associated with very serious complications. Intra cytoplasmic sperm injection increases the rate of monozygotic twinning and conjoined twins. Counseling with parents before IVF is very important

Hypomethylation of the miRNA-34a gene promoter is associated with Severe Preeclampsia

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

The association of pri-miRNA- 26a1 rs7372209 polymorphism and Preeclampsia susceptibility

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

Association of the placental VEGF promoter polymorphisms and VEGF mRNA expression with preeclampsia

Background: Preeclampsia (PE), is a pregnancy-specific complication with the placental origin which associated with altered expression of angiogenic factors. Vascular Endothelial Growth Factor (VEGF), is a growth and hypoxia-induced factor which contributes to the regulation of various processes. The present study has investigated the association of the placental VEGF −634G/C (rs2010963), −1154G/A (rs1570360), and −2549 I/D (18bpindel) polymorphisms in the promoter region with VEGF mRNA expression in PE women and control group. Methods: This case-control study was performed on the placenta of 84 PE women and 103 controls after delivery. Genotyping of the VEGF polymorphisms was done by PCR or PCR, PCR-RFLP or sequencing methods. The mRNA expression levels were measured by Quantitative Real-Time PCR. Results: The relative mRNA expression of VEGF gene was significantly higher in PE women compared to controls. The relative mRNA expression of VEGF gene was significantly higher in women with −634CC genotype compared to CG + GG genotypes in PE women and total studied women but not in control women. However, there was no association between the placental VEGF −1154G/A and −2549 I/D polymorphisms and VEGF mRNA expression neither in PE nor in control groups. Conclusion: 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

The placental vascular endothelial growth factor polymorphisms and preeclampsia/preeclampsia severity

Preeclampsia (PE) is a serious pregnancy-specific condition, which originates from placenta and finishes after delivery. The present study has investigated the association between placental VEGF I/D (rs35569394), −1154G/A (rs1570360), and −634G/C(rs2010963) polymorphisms and maternal VEGF −2549 I/D (rs35569394) polymorphism with PE and PE severity. In this case-control study, the maternal blood of 217 women with PE and 210 normotensive pregnant women and the placenta of 84 PE women and 103 normotensive women were collected after delivery. Genotyping was done by PCR or PCR-RFLP methods. The maternal VEGF-2549I/D genotypes were not associated with PE or PE severity. The placental VEGF −2549 I/D genotypes were not associated with PE too; however; the placental VEGF-2549 DD genotype was statistically different between women with severe PE and mild PE or the controls. The placental VEGF −634GC and CC genotypes were significantly higher in PE women and associated with 2.6 and 2-fold higher risk of PE, respectively. The VEGF −634GC and CC genotypes were associated with PE severity. No association was found between placental VEGF −1154G/A polymorphism and PE or PE severity. The placental DGC haplotype of VEGF −2549 I/D, −1154G/A, and −634G/C polymorphisms was associated with 2.9-fold higher risk of PE. However, the placental IAG haplotype was associated with 0.3-fold lower risk of PE. In conclusion, the placental VEGF −2549 DD genotype was associated with severe PE and the placental −634GC and CC genotypes were associated with PE and severe PE. No association was found between VEGF −1154G/A polymorphism and PE or PE severity