THE ROLE OF CHEMOKINE GENES IN THE DEVELOPMENT OF ADENOMYOSIS WITH CONCURRENT ENDOMETRIAL HYPERPLASTIC PROCESSES

Relevance: Adenomyosis and endometrial hyperplastic processes (EHPs) are among the leading problems in gynecology. The causes and underlying mechanisms of the concurrent development of adenomyosis and EHPs are studied by various research teams. Hormonal and genetic disorders are known to be involved in the development of this pathology. Chemokines are involved in angiogenesis, hematopoiesis, embryological development, B-and T-cell development, dendritic cell maturation, inflammation, infection, tumor growth and metastasis, so they may be associated with the development of adenomyosis and its combination with EHPs. The role of intergenic chemokine gene interactions in the formation of this disease remains poorly understood. Objective: To investigate the relationship between chemokine genes and adenomyosis with concurrent EHPs. Materials and methods: The study included 91 women with adenomyosis and concurrent EHPs and 789 control women. Genotyping of six chemokine genes SDF1 c.*519 G>А rs1801157, RАNТES c.-471 G>А rs2107538, I-ТАС c.*1539 Т>С rs4512021, МСР1 c.77-109 G>С rs2857657, МIР1β c.*524 А>Т rs1719153, IL-8 c.-352 А>Т rs4073 was performed by real-time PCR. The odds ratio (OR) and the 95% confidence interval (CI) were used to evaluate associations. ARSampler software was used to assess the association of combinations of alleles and genotypes of the analyzed genes with the development of adenomyosis with concurrent EHPs. Results: Associations of the studied genes with the development of the disease were revealed. Patients with adenomyosis and concurrent EHPs were more likely to have the T allele of the rs4073 IL-8 gene (86/142, 60.56%) than controls (379/744, 50.94%; p=0.04, OR=1.48 95% CI 1.02–2.40). The prevalence of the rs1801157 SDF A allele (38/152, 25.0%) was higher compared with controls (126/730, 17.26%; p=0.03, OR=1.59 95% CI 1.06–2.40). The combination of TT genotype rs4073 IL-8 with A allele rs1801157 SDF1, A allele rs4512021 I-TAC, and G allele rs2857657 MSR1 (OR=4.55, 95% CI 2.10–9.86, p=0.0002) was a risk factor for disease. The combination of the A allele rs4073 IL-8 with the G allele rs2107538 RANTES and the T allele rs1719153 MIR1β is protective against the development of adenomyosis with concurrent EHPs (OR=0.36 95% CI 0.18–0.73, p=0.002). Conclusion: Polymorphic chemokine gene loci SDF1 c.*519 G>A rs1801157, RANTES c.-471 G>A rs2107538, I-TAS c.*1539 T>C rs4512021, MSR1 c.77-109 G>C rs2857657, MIR1β c.*524 A>T rs1719153, IL-8 c.-352 A>T rs4073 are associated with the development of adenomyosis with concurrent EHPs. © A group of authors, 2022.