Investigating the Association between SNPs in AGT Gene with Preeclampsia: A In silico Study

Preeclampsia (PE) is a pregnancy disorder characterized by hypertension and proteinuria [۱].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 [۲]. Insilico studies can help to identify effective single nucleotide polymorphisms (SNPs) in the structure andstability of AGT protein and could predict their association with PE. In this study, missense SNPs of theAGT gene and their effects on PE were investigated. At first, all common missense SNPs of the AGTgene monitored. Missense SNPs with a minor allele frequency (MAF)≥ ۰.۱ were selected in the NCBIdbSNPdatabase. The effect of each selected SNPs based on functional, structural, and stability aspectsof the protein and mRNA were investigated by nine following online software: SIFT, Polyphen-۲,PantherDB, PROVEAN, I-mutant, iStable, MUpro, HOPE, PSIPRED. Analysis of missense SNPs bySIFT, Polyphen-۲, and PantherDB showed that rs۴۷۶۲ (G>A, Thr۱۹۸Met) could be as a deleteriousSNP. The prediction of the effects of this SNP by I-mutant, iStable, MUpro, and PSIPRED also showedsubstitution of Thr۱۹۸Met may decrease the stability of the protein. Angiotensin protein is expressed inthe 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 physiologicallyactive enzyme angiotensin II. Dysfunction of this protein can play a role in the pathogenesis ofhypertension and preeclampsia. Based on this study, the AGT gene may be involved in the developmentof PE and rs۴۷۶۲ is expected to be effective in function of this gene.

کلیدواژه ها:

Angiotensinogen ، Blood Pressure ، In silico analysis ، Missense SNPs ، Preeclampsia