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

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

Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study

Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk

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