Unraveling the Causal Linkages of RBP7 and SCGB3A1 on Pelvic Organ Prolapse: Multifaceted Insights From Genome-Wide Mendelian Randomization, Single-Cell RNA Analysis, and Network Pharmacology.

BACKGROUND

Pelvic organ prolapse (POP) is a common pelvic floor disorder in middle-aged and elderly women. Its pathophysiology is complex, involving weakened pelvic floor muscles and connective tissues. There is a need to explore its underlying pathogenesis and develop effective treatments.

METHODS

We integrated single-cell sequencing (scRNA-seq) data analysis with Mendelian randomization (MR) analysis. scRNA-seq data of vaginal mucosal tissue were obtained from individuals with and without pelvic organ prolapse (POP); we then performed dimensionality reduction and cell subset identification. MR was conducted using GWAS summary statistics and eQTL data, following STROBE-MR guidelines. We also performed protein-protein interaction analysis, functional enrichment analysis, drug prediction, and molecular docking.

RESULTS

We identified RBP7 as a POP risk factor and SCGB3A1 as a protective factor. RBP7 high expression increased POP risk (IVW, OR 1.262, 95% CI 1.093-1.459, p = 0.002), whereas SCGB3A1 high expression decreased it (IVW, OR 0.907, 95% CI 0.844-0.975, p = 0.008). We found associated key genes and their biological processes and signaling pathways. We also predicted potential drugs and their binding affinities.

CONCLUSION

The study highlights the significance of fibroblast gene expression changes in collagen metabolism for POP. It identified risk and protective genes and explored potential drugs. Future research should verify SCGB3A1 functions in fibroblasts, conduct preclinical drug trials, and clarify POP molecular mechanisms.