The miR-17-92 cluster is composed of seven miRNAs (microRNAs; miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92a-1). Previous studies have indicated that this cluster is involved in cell proliferation and their overexpression has been seen in several types of cancer. We have assessed the overexpression effects of miR-17-92 on the expression of several genes associated with cell-cycle regulation. The human miR-17-92 gene was cloned into a transposone-based vector, piggyBac and transfected into HEK-293T [HEK-293 cells (human embryonic kidney cells) expressing the large T-antigen of SV40 (simian virus 40)] cell line. Gene expression analysis indicated that up-regulation of this cluster causes significant changes in the expression of several cell-cycle related genes, including CDK2 (cyclin-dependent kinase 2), cyclin-D2, c-Myc and CREB (cAMP-response-element-binding protein). Other methods of transcripts assessment confirmed miR-17-92 overexpression enhances cell proliferation.
Objective
Preeclampsia (PE) is a life‐threatening complication of pregnancy that accounts for 12% of all maternal deaths worldwide. The aim of this study is to investigate the relationships between the polymorphisms of angiotensinogen (AGT) gene and preeclampsia.
Material and methods
In this study, 240 unrelated preeclampsia patients and 178 normotensive women were examined. Genomic DNA was extracted then we assessed M235T(C/T) and A‐6G polymorphisms of the AGT gene. Genotyping of M235T and A‐6G polymorphisms were performed using SSP‐PCR and MS‐PCR, respectively.
Results
A significant protective association was observed between A‐6G G allele, A‐6G A/G heterozygote genotype (OR = 0.6, p = 0.007 and OR = 0.6, p = 0.04) against PE. Furthermore, it was shown that two copies of A‐6G A allele would increase PE risk (OR: 0.62, p = 0.04). Our results did not show a significant association for M235T polymorphism and PE. However, the combinations of A‐6G A/A genotype and M235T T/C genotype (OR = 0.4, p = 0.02) and also A‐6G A/G genotype and M235T T/C genotype (OR = 0.5, p = 0.04) in controls represented a significant protective association against PE.
Conclusion
According to the existence of significant correlation between two candidate polymorphisms, A‐6G and M235T polymorphisms, with PE disease in our study, they may be considered as valuable factors in susceptibility to PE disease in Iranian women.
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