In silico study of gene-gene interaction of PIK3R1and PIGF deleterious SNPs in correlation to the preeclampsia risk and its haplotype effect on antihypertensive treatment

Abstract

Introduction: The PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) and PlGF (Placenta growth factor)genes share some common pathways with eNOS,( Endothelial nitric oxide synthase) that plays a vital role in angiogenesis of blood vessels and regulating endothelial function. The PIK3R1 gene encodes the receptor for the p85α regulatory subunit of the phosphoinositide-3-kinase (PI3K), that involved in endothelial cell migration. The PlGF gene encodes for the placenta growth factor, a homolog of vascular endothelial growth factor (VEGFA) that is involved in angiogenesis. PIK3R1 and/or PlGF mutations may cause dysregulation of eNOS contributing to endothelial dysfunction in preeclampsia. This study aims to analyze the effect of mutation of the PIK3R1 and PlGF genes on the structure and function of PIK3R1 and PGF protein that may have an important role in pathogeneses of preeclampsia. Methodology: The data on human PIK3R1and PGF genes were retrieved from dbSNP/NCBI. Ten prediction algorithms; SIFT, PROVEAN, Polyphen, SNAP2, SNPs&GO, PANTHER PhD-SNP, I-Mutant, Mutpred, and Hope were used to analyzing the effect of nsSNPs on functions and structure of the PGF and PIK3R1 protein. STRING and KEGG databases were used for PGF and PIK3R1 protein-protein interaction. Results and Discussion: As per the dbSNP database, the humanPIK3R1gene contained 365 missense mutations. A total 3nsSNPs (T239M, S229W, E47K) and 2 nsSNPs (H125Y, V59G) were predicted to have the most damaging effects on the structure and function of PIK3R1 and PGF respectively. STRING and KEGG revealed that PIK3R1and PGF had strong interactions with proteins involved in the VEGF signaling pathway and PI3K-Akt signaling pathway. PIK3R1 is confirmed to be linked to important diseases like preeclampsia and can affect its treatment response. Conclusion: Gene-gene interaction is an important factor in preeclampsia treatment, effect of mutation of the PIK3R1 and PlGF genes on the structure and function of PIK3R1 and PGF protein may have an important role in pathogeneses of preeclampsia. Also, these are linked to its treatment effect. This document gives formatting instructions for authors preparing papers for publication in the journal. Authors are encouraged to prepare manuscripts directly using this template. This template demonstrates the format requirements for the Journal.