Matrix metalloproteinase-3 gene promoter polymorphisms: A potential risk factor for pelvic organ prolapse

Abstract

Pelvic organ prolapse (POP) is a common multifactorial condition. Matrix metalloproteinases (MMPs) are enzymes capable of breaking down various connective tissue elements. Single-nucleotide polymorphisms (SNPs) in regulatory areas of MMP-encoding genes can alter their transcription rate, and therefore the possible effect on pelvic floor supporting structures. The insertion of an adenine (A) base in the promoter of the MMP-3 gene at position −1612/−1617 produces a sequence of six adenines (6A), whereas the other allele has five (5A). The aim of the present study was to investigate the possible association of MMP-3 gene promoter SNPs with the risk of POP. The patient group comprised 80 women with clinically significant POP [Stage II, III or IV; POP quantification (POP-Q) system]. The control group consisted of 80 females without any or important pelvic floor support defects (Stages 0 or I; POP-Q system). All the participants underwent the same preoperative evaluation. SNP detection was determined with whole blood sample DNA analysis by quantitative polymerase chain reaction (PCR) in LightCycler® PCR platforms, using the technique of sequence-specific hybridization probe-binding assays and melting temperature curve analysis. The results showed there was no statistically significant difference between 5A/5A, 5A/6A and 6A/6A MMP-3 gene promoter variants in the two study groups (P=0.4758). Therefore, MMP-3 gene promoter SNPs alone is insufficient to increase the genetic susceptibility to POP development.

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

“…Previous genetic analyses have revealed candidate genes associated with POP. These genes included collagen type I alpha (COL1A1) [4,5], collagen type III alpha 1 (COL3A1) [6], laminin gamma-1 (LAMC1) [7], and matrix metalloproteinases (MMPs) [8], which are all enrolled in extracellular matrix (ECM) pathways. The latest review comprehensively summarized and identified genetic polymorphisms associated with POP, including steroid hormone receptor genes and collagen/elastic fiber synthesis genes [5].…”

“…MMPs are a family of multiple catabolic proteases involved in the degradation of collagen fibers and other components of ECM. Several previous studies have identified the existence of polymorphisms in the promoter regions of MMP1, 3, and 9 genes, which could alter the expression of these genes and increase the risk of POP [8][9][10][11]. Chen et al [12] detected three MMP9 SNPs (rs3918242, rs17576, and rs2250889) and found rs17576 to be associated with POP.…”