Pelvic floor disorders: linking genetic risk factors to biochemical changes

• Published in: BJU international Vol. 108; no. 8; pp. 1240 - 1247
• Main Authors: Campeau, Lysanne, Gorbachinsky, Ilya, Badlani, Gopal H., Andersson, Karl Erik
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011; Wiley-Blackwell
• Subjects: Biological and medical sciences; collagen; Collagen - genetics; Collagen - metabolism; elastin; Elastin - genetics; Elastin - metabolism; Extracellular Matrix - metabolism; Female; Genetic Predisposition to Disease; Humans; matrix metalloproteinase; Matrix Metalloproteinases; Medical sciences; Nephrology. Urinary tract diseases; Pelvic Floor - pathology; pelvic floor disorder; pelvic organ prolapse; Pelvic Organ Prolapse - genetics; Pelvic Organ Prolapse - metabolism; Risk Factors; stress urinary incontinence; Urinary Incontinence, Stress - genetics; Urinary Incontinence, Stress - metabolism; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Nephrology; Metalloendopeptidases; Biochemistry; pelvic floor disorder; Genetic determinism; Epidemiology; pelvic organ prolapse; Urology; Voiding dysfunction; Pelvic cavity; Urinary system disease; stress urinary incontinence; Enzyme; Elastin; Glycoprotein; Urinary tract disease; Prolapse; Genetic disease; Prolapsus; Peptidases; Pelvic floor; Collagen; Risk factor; Hydrolases; matrix metalloproteinase; Bladder disease; Urinary stress incontinence; Organ
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10385.x

What's known on the subject? and What does the study add? Pelvic floor disorders are associated with altered biochemical composition and structure of pelvic tissue. Epidemiological studies have postulated a genetic contribution to pelvic floor disorders. Certain biochemical changes can be explained by candidate genes and polymorphism involved in the expression of ECM‐related proteins. Pelvic floor disorders (PFDs) such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) may share a common pathophysiological process related to pelvic floor tissue laxity and loss of support. We reviewed recent literature on observed biochemical changes in women with SUI and POP, linking them to genetic predisposition. We found that studies of pelvic tissues showed differences between control subjects and women with POP and SUI in collagen and elastin structure at a molecular and fibrillar level. Studies were heterogeneous but showed a trend towards decreased collagen and elastin content. The contribution of matrix metalloproteinases to increased collagenolysis can be related to genetic polymorphisms present in higher frequency in women with PFD. Extracellular matrix (ECM) protein turnover plays a role in the development of POP and SUI, but much remains to be understood of this complex dynamic interplay of enzymes, proteins and molecules. Genotyping of candidate genes participating in ECM formation will elucidate the missing link between the manifestation of the disease and the biochemical changes observed systematically, in addition to those in the pelvic floor.