In Silico Determination of Changes in Transcription Factor Binding Sites for the Preeclampsia Risk Haplotype in the Regulatory Region of the FLT1 Gene

Abstract

Preeclampsia (PE) is one of the most common complications of pregnancy that occurs in 3–8% of pregnant women, being one of the top five causes of maternal morbidity and mortality. We found that PE-associated polymorphisms near the FLT1 gene are located in the same regulatory region. In combination, these polymorphisms can form a genetic pattern which affects the development of the pathology by forming a PE risk haplotype. When analyzing the changes in TPFS, which are characteristic only for the risk haplotype with a prevalence in the European population of 0.0825, we found that five TFBs change. The number of TFBSs for ELF1 and SPIB increases, whereas the number of TFBSs for POLR2A and KLF15 decreases (not expressed in the placenta).The newly emerged transcription factor binding site KAT5 acquires a promoter signature in the placenta only after 118 days of pregnancy, whereas before the 118th day, only the DNase signature is observed. Theoretically, the appearance of a new TFBS can increase the expression of FLT1, causing an imbalance of angiogenic/antiangiogenic factors, which is characteristic of PE.

Keywords

• preeclampsia SNP
• polymorphism
• FLT1
• risk haplotype
• TFBs
• TF