GENETIC ASPECTS OF ADVERSE CONSEQUENCES OF PREGNANCY WITH ISTHMIC-CERVINAL INSUFFICIENCY

Abstract

According to modern ideas, both physiological and pathological processes are the result of complex interactions of genetic and epigenetic factors. Among the publications of recent years, there are no studies on the connection of PROGINS and ESR1 gene polymorphisms or gene methylation with ICI and adverse pregnancy outcomes on its background, which prompted us to conduct research in this direction.
 The aim of the study. To assess the influence of genetic and eugenetic factors on adverse pregnancy outcomes in isthmic-cervical insufficiency (ICI).
 Research material and methods. comprehensively examined 20 pregnant women with ICI, the correction of which was carried out with the use of a cerclage (main group), in which 2 subgroups were distinguished: ICI1 - 10 women with ICI and an unfavorable end of pregnancy (miscarriage before 22 weeks of pregnancy in 4 women and premature birth in 6 patients ) and ICI2 – 20 patients in whom delivery was urgent (after 37 weeks).
 A molecular genetic analysis of PGR gene variants (Alu insertion), ESR1 (A351G, rs 9340799) and an epigenetic study of methylation of the promoter region of the estrogen receptor α (ESR1) gene was performed.
 The results. Loss of pregnancy and premature birth in ICI can be caused not only by a decrease in hormone levels, but also by a violation of hormonalreceptive relationships. The probability of genetic conditioning of disorders of receptive progesterone and estrogen mechanisms in patients with ICI has been established. The presence in a pregnant woman of the mutant T2 allele of the PGR polymorphism (Alu-insertion) and the combination of homozygous genotypes T2T2+ GG of the polymorphic variants of the PGR (Alu-insertion) and ESR1 (A351G rs9340799) genes can be markers of a high risk of adverse pregnancy termination in ICI. In addition, the change in gene expression can be caused by epigenetic disorders, namely gene methylation: hypermethylation of the promoter region of the estrogen receptor α (ESR1) gene was detected in 40% of women with ICI and pregnancy loss in the II trimester or premature birth, which is 4 times higher than the rate women with ICI and normal termination of pregnancy.
 Conclusions. Adverse pregnancy outcomes with ICI can be caused by genetic (presence of a mutant T2 allele of the PGR polymorphism and combinations of homozygous T2T2+ GG genotypes of polymorphic variants of the PGR Alu-insertion and ESR1 A351G genes) and epigenetic factors (hypermethylation of the promoter region of the estrogen receptor α ESR1 gene). However, these results are preliminary and require further indepth studies on larger data samples.