Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse

Ferrari, María Rosa; Rossi, Gabriela R.; Biondi, Maria Luisa; Viganò, Paola; Dell'Utri, Chiara; Meschìa, Michele

doi:10.1007/s00404-011-2199-9

Cited by 43 publications

(81 citation statements)

References 30 publications

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“…The authors found that two genetic polymorphisms of MMP-9 were significantly associated with prolapse risk (OR: 5.41 and 5.77). These findings contradict the results of an Italian study, 64 which found no difference in MMP-9 expression between the prolapse and the control groups. However, there was a positive association between a single variation of MMP-1 and prolapse.…”

Section: Regulators Of Collagencontrasting

confidence: 99%

“…[57][58][59][60][61][62][63][64] Nucleotide polymorphisms in the COL3A1 genes are associated with prolapse, thus suggesting the role of defective collagen III in the genesis of prolapse. [57][58][59] Interestingly, type IV Ehlers-Danlos syndrome is due to mutations in the same COL3A1 gene.…”

Section: Regulators Of Collagenmentioning

confidence: 99%

“…60,61 A mutation in the gene expressing MMP is also associated with prolapse. [62][63][64] Chen et al, 62 conducted a case-control study in Taiwanese women with prolapse (n = 92) versus control (n = 152). The authors found that two genetic polymorphisms of MMP-9 were significantly associated with prolapse risk (OR: 5.41 and 5.77).…”

Section: Regulators Of Collagenmentioning

confidence: 99%

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Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Lim

Khoo

Wong

et al. 2014

Aust NZ J Obst Gynaeco

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Gynaecologists are becoming increasingly aware that women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. In the past five years, several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This review examines the contemporary evidence regarding the role of collagen in prolapse.

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Section: Regulators Of Collagencontrasting

confidence: 99%

Section: Regulators Of Collagenmentioning

confidence: 99%

Section: Regulators Of Collagenmentioning

confidence: 99%

See 1 more Smart Citation

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Lim

Khoo

Wong

et al. 2014

Aust NZ J Obst Gynaeco

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“…In another study, urinary collagenase assay of factors including MMP-1, -2 and -9 was the optimum pre-operative predictor of mid-urethral sling outcome in women with SUI, and revealed negative correlation with urethral closure pressure (20,21). Recent genotypic studies have identified molecular markers of dysfunction of the supportive pelvic floor connective tissue, with genetic polymorphism of MMP-1 and -9 identified in women with POP compared with controls (22,23). Studying the genetic markers of ethnic risk for pelvic floor dysfunctions including MMP polymorphism in a population of healthy and nulliparous multi-ethnic women could similarly contribute to early detection and prevention of these disorders (22,23).…”

Section: Discussionmentioning

confidence: 99%

“…Recent genotypic studies have identified molecular markers of dysfunction of the supportive pelvic floor connective tissue, with genetic polymorphism of MMP-1 and -9 identified in women with POP compared with controls (22,23). Studying the genetic markers of ethnic risk for pelvic floor dysfunctions including MMP polymorphism in a population of healthy and nulliparous multi-ethnic women could similarly contribute to early detection and prevention of these disorders (22,23). Identification of at-risk women with increased plasma MMP/TIMP ratio may be supported by further genetic evidence of polymorphism, using a simple blood test at a young age prior to first pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Circulating matrix metalloproteinases and their tissue inhibitors as markers for ethnic variation in pelvic floor tissue integrity

et al. 2018

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Abstract. The purpose of the present study was to measure the plasma levels of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP)-1 and -2, as surrogate biomarkers for pelvic floor tissue integrity in young, healthy multi-ethnic women. This was hoped to elucidate ethnic vulnerability to support-related pelvic floor dysfunctions. The plasma levels of MMP-2 and -9 and TIMP-1 and -2 were measured by sandwich ELISA in nulliparous, young (18-29 years) women volunteers (n=85) from five ethnic groups [n=17/group; Bahrainis, other Arabs, Filipinos, Indians/Pakistanis and Caucasians (Italians)] and compared with levels in Italians as the reference group. It was identified that the levels of plasma MMP-2 were significantly higher in Italians than in Bahrainis (P<0.001) and Filipinos (P<0.001), but significantly lower than in Indians/Pakistanis (P=0.013); whereas, the levels of plasma MMP-9 were significantly higher in Italians than in Bahrainis (P=0.009) and Indians/Pakistanis (P<0.015). The levels of plasma TIMP-2 were significantly lower in Italians than in Indians/Pakistanis (P=0.003), but the levels of plasma TIMP-1 were significantly higher in Italians than in all other groups (P<0.05) excluding Bahrainis. Although MMP-2 correlated negatively with TIMP-2 and MMP-9 correlated positively with TIMP-1, both correlations were not significant (r=0. 071, P=0.533 and r=0.197, P=0.8, respectively). In all ethnic groups, MMP-9 level correlated positively with BMI (r=0.26, P=0.02), and TIMP-2 level with age (r=0.23, P=0.045). Overall, the trends for higher levels of MMP-2 and -9 and lower levels of TIMP-2 in the plasma of Caucasian women may indicate a greater tendency for collagenolysis and weaker connective tissue with increased risk of developing pelvic floor dysfunctions, and thus may potentially serve as biomarkers for pelvic floor tissue integrity. IntroductionSupport-related pelvic floor dysfunctions including pelvic organ prolapse (POP), stress urinary incontinence (SUI) and faecal incontinence are caused by structural defects in the complex supportive apparatus formed by the connective tissue and striated muscles of the pelvic floor (1-7). The role of the connective tissue component is to counteract both stretch and compression of the pelvic floor exerted by the gravitational and inertial forces of the intra-abdominal pressure and to repair damaged tissues (2,4,6). This supportive function is determined by the tensile strength of collagen in the extracellular matrix that is maintained by continuous remodelling of collagen (1,3). The latter depends on a critical balance between collagen degradation and production that is controlled by a group of enzymes, matrix metalloproteinases (MMPs) and their respective tissue inhibitors (TIMPs) (1,3,5). The prevalence of support-related pelvic floor dysfunctions is affected by racial and ethnic origin, with a higher risk observed in Caucasians than in other populations (8)(9)(10). This may be explained by genetic, environmental and/or anatomical difference...

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Serum proteomic pattern in female stress urinary incontinence

et al. 2018

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The pathophysiology of Stress Urinary Incontinence (SUI) is poorly understood. The aim of this study was to identify the serum proteomic profile in patients with SUI and to replicate findings from a preceding study in which a significant difference in the urinary proteome was identified. Serum samples were collected from 38 patients (19 SUI; 19 matched, continent controls). Sample preparation included serum albumin depletion, in-solution enzymatic digestion of proteins applying a combination of Gluc-C and trypsin and peptide separation using nano High Performance Liquid Chromatography. Label-free quantitation of peptides and proteins was performed after triplicate measurements using quadrupole time-of-flight mass spectrometry. Peptide identification was achieved by searching the Human SwissProt Database using Mascot and X!Tandem. Main outcome measure was the relative abundance of each detected protein in serum. Of 7012 identified proteins, 33 proteins were induced (detected in SUI, not in controls) and five proteins were depleted (detected in controls, not in SUI). All depleted proteins play a role in immune/DNA damage response. Induced proteins are involved in inflammatory response, response to cellular stress, coagulation and cytoskeleton stability/ motility. Plasma serine protease inhibitor (SERPINA5) was found induced and previously also showed a higher abundance in urine samples of SUI patients. Data are available via ProteomeXchange with identifier PXD008553.

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Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse

Abstract: Our findings suggest that the polymorphism of metalloproteinases-1 might have a role in mediating susceptibility to pelvic organ prolapse.

Cited by 43 publications

References 30 publications

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Circulating matrix metalloproteinases and their tissue inhibitors as markers for ethnic variation in pelvic floor tissue integrity

Serum proteomic pattern in female stress urinary incontinence

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