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چکیده
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Preeclampsia (PE) is a common pregnancy specific disease, that presents with hypertension after the 20th week of pregnancy. Multiple genes or single nucleotide polymorphisms (SNPs) may contribute to the incidence and development of PE. Endothelins (EDNs) are a peptide family that induces the DNA replication and cell growth in various tissues, which mainly regulate vascular tone, angiogenesis, and mitosis procedures. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. In silico studies can help to identify effective single nucleotide polymorphisms (SNPs) in the structure and function of EDN1 protein and could predict their association with PE. In this study, missense SNPs of the EDN1 and their effects on PE were investigated. At first, all common missense SNPs of the EDN1gene monitored. Missense SNPs with a minor allele frequency (MAF)≥ 0.1 were selected from the NCBI-dbSNP database. The effect of each selected SNPs based on functional, structural, and stability aspects of the protein were investigated by the nine following online software: SIFT, Polyphen-2, PantherDB, PROVEAN, I-mutant, iStable, MUpro, HOPE, and PSIPRED. Analysis of missense SNPs by SIFT, Polyphen-2, and PantherDB showed that rs5370 (G>T, Lys198Asn) could be as a deleterious SNP. The prediction of the effects of this SNP by I-mutant, iStable, MUpro, and PSIPRED also showed that the substitution of Lys198Asn may decrease the stability of the protein. Based on this study, EDN1-rs5370 polymorphism could be correlated with the increased risk of PE.
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