Genetic Association Study in Women with Pelvic Organ Prolapse

Hypothesis / aims of study Pelvic organ prolapse (POP) is a common yet distressing pelvic floor dysfunction affecting one-third of adult women worldwide. However, the underlying pathophysiology is largely unknown. Its etiology is multifactorial, including direct mechanical injury, partial denervation of pelvic floor, and hormonal changes caused by pregnancy. Findings from epidemiologic studies suggest that occurrence of POP can be attributed to genetic factors. Endothelin-1 (EDN-1) is a potent vasoconstrictor and accumulating evidence showed that endothelin-1 plays an important role in vascular pathophysiology and wound repair. Among the polymorphisms reported in EDN1, clinical studies demonstrated that Lys allele carrier status at codon Lys198Asn (G/T, rs5370) was related to higher levels of plasma EDN1 among women during pregnancy. Another sequence variant, the 3A/4A polymorphism (-134delA; rs10478694) located in the 5’-untranslated region, has also been found to be significantly different in plasma EDN1 levels between individuals with the 3A/3A and 3A/4A genotypes. Because EDN1 induces collagen matrix contraction and stimulates mitogenesis of myofibroblast and fibroblast in vitro, we postulate that genetic variations in EDN1 could lead to alterations in EDN1 protein expression and affect the mechanical and contractile properties of pelvic floor myofibroblasts in women with pelvic organ prolapse (POP).