GENETIC RISKS OF DEVELOPMENT OF PELVIC ORGAN PROLAPSE RECURRENCE AFTER HYSTERECTOMIES

Objective: to establish immunohistochemical and genetic markers of POP on the basis of studying of features of connecting tissue of women with a disease recurrence. Materials and methods. The study involved 168 women, 134 of them with POP relapses aged 35 to 65 (96 after hysterectomy by vaginal access because of a total and partial uterus and vaginal walls prolapse). The control group consisted of 44 women aged 35-52 with no POP signs, after abdominal hysterectomy for uterine fibroids, adenomyosis, endometrial pathology. Used: immunohistochemical (to assess tissue biopsies of sacrum-uterine and round uterine ligaments), the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), genotyping by polymerase chain reaction of MMP/TIMP polymorphisms. Results: Disturbances in the expression of the most important CT disorganization markers in POP shall comply with the expression of protein coding genes, in particular - MMPs and TIMP. The results of studying the frequency of polymorphism genotypes in the groups of healthy women and those with POP are presented in chart. Associations with GP development have been established among women with genetic polymorphisms: 5A5A (rs3025058) MMP3 gene. Statistical significance for the groups was preserved after the correction for multiple comparisons. The low frequency of CC allele of MMP2 gene (735 C>T) among patients with POP gave reason to consider it as a marker of biodegradation reduction in tissues connecting the core of pelvic organs. The mutant CT allele of polymorphic variant rs 2277698 of TIMP-2 gene is more common among women with pelvic floor failure, but statistical significance was defined in relation to the protective CC genotype, revealed among half of healthy women. Reducing of TIMP-1 accumulation on the background of metalloproteinases high expression indicates a substantial role of dynamic equilibrium violation in pathobiochemical disorders and pelvic dysfunction. Conclusions. The determination of "risk" alleles predisposing to POP should be considered as a contribution to the understanding of the pathogenesis of the disease. They can be used as genetic markers of individual undifferentiated CT dysplasia manifestations. Molecular and biological characteristics of tissue remodeling in POP allow us to consider immunohistochemical diagnosis as an improved capability of disease recurrence risk prediction after surgery and the choice of optimal treatment technology.