ASSOCIATION OF I/D POLYMORPHISM OF THE ACE GENE WITH THE PRESENCE/ABSENCE OF UTERINE BLEEDING AND THE CHARACTERISTICS OF LEIOMYOMATOUS NODES IN PATIENTS WITH A COMORBID COURSE OF UTERINE LEIOMYOMA AND GENITAL ENDOMETRIOSIS
Authors: Vovk-Shulha S. , Khmil S. 
Published: April 2024

Uterine leiomyoma (UL) is the most common benign tumor, which leads to reduced work capacity and loss of reproductive function in women of childbearing age.The aim of the study – to investigate the presence of probable associations of the polymorphic variant I/D of the angiotensin-converting enzyme (ACE) gene with the presence/absence of uterine bleeding and the characteristics of leiomyomatous nodes in patients with a comorbid course of intramural UL and genital endometriosis.Study methods. The molecular genetic study of the polymorphic variant I/D of the ACE gene was applied to 33 patients with a comorbid course of intramural UL and genital endometriosis and 30 patients with isolated intramural UL (at the same time, 5 patients had a medical history of cycles of controlled ovarian stimulation with the help of assisted reproductive technologies and a diagnosis of infertility) according to the standard operating procedure developed in the interdepartmental educational and research laboratory of the Ternopil State Medical University named after I.Ya. Horbachevskyi of the Ministry of Health of Ukraine. Study results. In patients with isolated intramural UL, uterine bleeding probably prevails in individuals with the DD genotype of the polymorphic variant of the ACE gene relative to individuals with the ID and II genotypes (χ2=7.07; p=0.029). At the same time, the presence of the D allele increases the risk of uterine bleeding by 5.8 times. Analysis of the dominant pattern of inheritance of the ACE gene showed that carriers of the D allele (genotype ID+DD) among patients with isolated intramural UL have a 6.3-fold increased risk of uterine bleeding. Analysis of the relationship between the maximum diameter of the leiomyomatous node in patients of the studied groups and the I/D polymorphism of the ACE gene in the group with isolated intramural UL revealed that the maximum diameter of the node in carriers of the DD genotype exceeds the corresponding indicator in carriers of the II genotype by 28.89% (p <0.001), and the maximum node diameter in ID genotype carriers exceeds the corresponding indicator in II genotype carriers by 9.43% (р=0.032). In addition, the maximum node diameter is 14.29% greater in carriers of the D allele than the corresponding indicator in carriers of the I allele. As for the relationship between the number of leiomyomatous nodes in the patients of the studied groups and the I/D polymorphism of the ACE gene, probable differences were established only in the group with a comorbid course of intramural UL and genital endometriosis. At the same time, the individuals with a solid node predominate among carriers of the II and ID genotypes, while the individuals with multiple nodes predominate among carriers of the DD genotype; the distribution of persons with a solid node or multiple nodes is even among carriers of the D allele, and a solid node was found in 72.41% of individuals (р=0.045) among carriers of the I allele. In addition, the presence of the D allele increases the risk of multiple nodes by 3.09 times. Conclusions. It was found for the first time in the Ukrainian population, that the I/D polymorphism of the ACE gene (the presence of the D allele (genotype ID+DD)) is probably associated with an increased risk of multiple leiomyomatous nodes in patients with a comorbid course of intramural UL and genital endometriosis and with an increased risk of uterine bleeding and the size of the leiomyomatous node in patients with isolated intramural UL. The results of the logistic regression analysis show that the presence of the DD genotype of the ACE gene is associated with the development of uterine bleeding and the occurrence of multiple leiomyomatous nodes in patients with intramural UL, regardless of the presence of comorbid genital endometriosis.