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چکیده
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Preeclampsia (PE) is a pregnancy disorder characterized by hypertension and proteinuria [1]. The Angiotensinogen (AGT) protein is an important component of the rein-angiotensin system (RAS), a key regulatory system of blood pressure, which could be closely related to PE susceptibility [2]. In silico studies can help to identify effective single nucleotide polymorphisms (SNPs) in the structure and stability of AGT protein and could predict their association with PE. In this study, missense SNPs of the AGT gene and their effects on PE were investigated. At first, all common missense SNPs of the AGT gene monitored. Missense SNPs with a minor allele frequency (MAF)≥ 0.1 were selected in the NCBI- dbSNP database. The effect of each selected SNPs based on functional, structural, and stability aspects of the protein and mRNA were investigated by nine following online software: SIFT, Polyphen-2, PantherDB, PROVEAN, I-mutant, iStable, MUpro, HOPE, PSIPRED. Analysis of missense SNPs by SIFT, Polyphen-2, and PantherDB showed that rs4762 (G>A, Thr198Met) could be as a deleterious SNP. The prediction of the effects of this SNP by I-mutant, iStable, MUpro, and PSIPRED also showed substitution of Thr198Met may decrease the stability of the protein. Angiotensin protein is expressed in the liver and is cleaved by renin enzyme in response to blood pressure reduction. The resulting product, angiotensin I, is then cleaved by angiotensin-converting enzyme (ACE) to produce the physiologically active enzyme angiotensin II. Dysfunction of this protein can play a role in the pathogenesis of hypertension and preeclampsia. Based on this study, the AGT gene may be involved in the development of PE and rs4762 is expected to be effective in function of this gene.
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