The importance of polymorphism of the COL1A1 gene in the development of pelvic organ prolapse in women of childbearing age

Abstract

Pelvic organ prolapse (POP) is a chronic slowly progressive disease. One of the most significant risk factors for the formation of omissions and prolapses of the internal genitalia is connective tissue diseases. Type I collagen is the most common protein of the intercellular substance of connective tissue, mutation of the COL1A1 gene encoding it leads to the synthesis of a defective protein. The aim of our study was to investigate the significance of COL1A1 gene polymorphism in POP development and in the occurrence of relapses of the disease in operated patients of different age groups. Material and methods. The study included 68 patients with verified pelvic organ prolapse, divided into two age groups (n = 34 in each): the first group included women aged from 23 to 44 years, the second – aged from 46 to 72 years. In all patients, the presence of manifestations of undifferentiated connective tissue dysplasia (UCTD) was assessed, a laboratory study of the polymorphism gene COL1A1 was conducted and the content of type 1 C-terminal collagen peptide (β-CrossLaps) in venous blood was measures. Results and discussion. 86.8 % of the examined patients had clinical signs of UCTD. Statistical analysis indicates that there is a relationship of the frequency of UCTD detection and severity of manifestations with age: the age of the patients with moderate to heavy UCTD (38 [37; 41] years, median [lower quartile; upper quartile]) was statistically significantly lower than that of the women with light degree (45.5 [38; 62] years; p < 0.001 years) and without UCTD (56 [48; 65] years; p < 0.001). There were no statistically significant differences in the polymorphism of the COL1A1 gene between patients under 45 (1 group) and over 45 (2 group) (p = 0.25), however, there is a tendency to decrease the frequency of G/G and increase T/T types of polymorphism in women of reproductive age. In patients with recurrent POP after surgical treatment, G/G polymorphism was less common (p < 0.001) and G/T was more common (p = 0.04). The level of β-CrossLaps was higher than the normative level in 8.8 % of the examined women; in 2 cases of identified heterozygous (G/T) polymorphisms, its significant rise was noted. ROC analysis performed to identify the relationship between age, gene COL1A1 polymorphism, signs of UCTD and the level of β-CrossLaps indicates the effectiveness of the integrated use of these indicators as predictors of POP development in women of the reproductive period. Conclusions. The results of the study suggest that the features of gene COL1A1 polymorphism, the level of β-CrossLaps can serve as predictors of the development of POP in women of reproductive age with clinical manifestations of signs of UCTD. Complex of these indicators allows to develop a prognostic model of POP early manifestation.