Investigating the functional impact of WNT-4, VEGF-A and MMP-2 genetic polymorphism in Pakistani patients with endometriosis and fibroids

Abstract

Uterine fibroids and endometriosis are common gynecological disorders that significantly impact women's well-being as well as complex aetiologies. This study uses an in silico examination of three important genes WNT-4, VEGF-A, and MMP-2 to investigate their genetic foundation. By using sophisticated computational methods to find single nucleotide polymorphisms (SNPs), we were able to distinguish harmful variations using SNP predictors like SIFT, Polyphen2, and PROVEAN. Three significant SNPs in VEGF-A, twelve in MMP 2, and seven in WNT-4 were found by our research. The majority of these SNPs have a deleterious effect on protein stability, according to structural and stability analyses. SUMOylation, N-glycosylation, and phosphorylation alterations were further highlighted by post-translational modification studies. Notably, the relationship between endometriosis and fibroids and SNP rs121908651 in WNT-4 was studied. There was a significant correlation with uterine fibroids (p = 0.0001) and with endometriosis (p = 0.0026). There is the need for more studies using larger cohorts to validate these SNPs' involvement in disease susceptibility and to pinpoint possible targets for treatment.