The polymorphisms of extracellular matrix-remodeling genes are associated with pelvic organ prolapse

Abstract

Introduction and hypothesis Extracellular matrix (ECM) synthesis and metabolism abnormalities may influence the pelvic supporting system and lead to the occurrence and development of pelvic organ prolapse (POP). Genetic polymorphisms of such related genes have been increasingly studied. This study aims to explore the association between the single-nucleotide polymorphisms (SNPs) of genes encoding ECM processing enzymes (a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTSs]), ECM degrading enzymes (matrix metalloproteinases [MMPs]) and their tissue inhibitors of metalloproteinase (TIMPs), and POP. Methods We conducted an association study including 48 women with POP at stages III and IV and 48 women without prolapse in Chinese groups. SNPs were identified using the target region sequencing technique. We performed Fisher’s exact tests to assess the association between SNPs and POP in the unadjusted model and logistic regression analysis in the adjusted model, adjusting for delivery and pregnancy. Results There was a significant association between TIMP2 SNP rs2277698 (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16–0.82; P = 0.015), ADAMTS13 SNP rs149586801 (OR, 0.18; 95% CI, 0.05–0.69; P = 0.012), and ADAMTS1 SNPs rs370850 and rs422803 (OR, 3.71; 95% CI, 1.35–10.15; P = 0.011 for both), rs402007, rs428785, rs434857, and rs445784 (OR, 2.18; 95% CI, 1.05–4.56; P = 0.038 for the four), and POP in the adjusted model. Conclusion TIMP2, ADAMTS13, and ADAMTS1 might be candidate genes for POP. Our results provide preliminarily new evidence for future investigation of these genes in the pathophysiology of POP.

Bioinformatic analysis of biological changes involved in pelvic organ prolapse

“…In addition, the steady state of ECM is an important factor for maintaining the normal distribution of pelvic organs. [14] In this study, upregulated genes in the POP group were found to be mainly enriched in CCs such as collagen-containing extracellular matrix, external encapsulating structure, and extracellular matrix.…”

FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway

“…The abnormality of its synthesis and metabolism affects the whole pelvic floor system, leading to the occurrence of POP. [ 19 ] ECM is formed by Collagen, elastin, glycoproteins, and proteoglycans. [ 20 ] Collagens, including Collagen I and III, provide tensile strength and integrity to the pelvic floor.…”

Long-term menopause exacerbates vaginal wall support injury in ovariectomized rats by regulating amino acid synthesis and glycerophospholipid metabolism

“…In addition, cytokine−cytokine receptor interactions, the PI3K-Akt signaling pathway, and the MAPK signaling pathway was also enriched, which have close regulatory effects on cellular mechanical properties (10,11). Zhu et al demonstrated that abnormal ECM synthesis and metabolism affected the pelvic support system, which led to the occurrence and progression of POP (12). Moreover, in our recent studies, we constructed focal adhesion signaling pathway-related ceRNA networks in POP by transcriptome analysis, which were found to be associated with mechanical properties (13).…”

“…Zhu et al. demonstrated that abnormal ECM synthesis and metabolism affected the pelvic support system, which led to the occurrence and progression of POP ( 12 ). Moreover, in our recent studies, we constructed focal adhesion signaling pathway-related ceRNA networks in POP by transcriptome analysis, which were found to be associated with mechanical properties ( 13 ).…”