Abstract:
Endometriosis and fibroids stand as the leading health problems related to reproduction in
women. In that sense, the present study was conducted to unravel genetic factors and single
nucleotide polymorphisms (SNPs) in the genes of ESR1, FSHB, and HOXA10, which have
been identified to play vital roles in these diseases. We have examined the missense variants
for their effects on the respective proteins using six in silico tools: SIFT, PolyPhen-2, Provean,
Panther, SNP&Go, and Predict SNP. The studies for effects on protein stability were done by
MutPred2, I-Mutant, MuPro, and structural modeling. The evolutionary conservation was
calculated by Consurf and PTMs were analyzed. Protein-protein interactions were investigated
using STRING, and gene-gene interaction was studied using GeneMANIA. In view of these
deep analyses, the ESR1 SNP rs121913044 (V364E, T > A) was selected for further in vitro
validation. It is through the association testing using ARMS PCR of the rs121913044 SNP with
endometriosis and fibroid blood samples from Rawalpindi and Islamabad that obtained a highly
significant association with the former disease with p = <0.0001 and significant of association
with the latter, fibroids, with a p-value of 0.0191. Therefore, this integrated approach gives
significance to computational and experimental methods in better understanding reproductive
diseases.
