Abnormal uterine bleeding in obese patients and polymorphisms of the eNOS, VEGF-A and HIF-1A genes
AbstractThe aim of the study was to investigate the frequency of occurrence of single-nucleotide polymorphism of VEGF-A, eNOS and HIF-1A genes and to assess their possible role in the development of endometrial dysfunction in women of reproductive age with abnormal uterine bleeding (AUB) and obesity.
Material and methods. 67 patients aged 23–48 years with AUB who meet the inclusion criteria were examined. Women were stratified depending on the presence of obesity: group I (n=37) – patients with a BMI ≥30 kg/m2, group II (n=38) – normal weight (BMI=18.5–24.9 kg/m2). All patients underwent a molecular genetic study of single-nucleotide polymorphism of VEGF-A (rs2010963), HIF-1A (rs11549465) and eNOS (rs2070744) genes. STATISTICA 8.0 and IBM SPSS Statistics v.26 (IBM Corporation, USA) programs were used for statistical data analysis. Quantitative indicators having an abnormal distribution were described using the median (Me), the interquartile range (IQR%) was taken into account. Comparison of groups on a categorical basis in the analysis of four-field conjugacy tables was performed using the exact Fisher criterion or the Pearson criterion χ2. The differences were found to be significant at p<0.05. The odds ratio indicator (OR) was calculated with 95% CI boundaries, indicators greater than one indicated the presence of significant differences.
Results. It was found that in women of reproductive age with obesity and AUB, compared with normal-weight and AUB, the heterozygous genotype of TS according to eNOS (rs2070744) is significantly more common (70.3 vs 40.0%, respectively, p=0.013). On the contrary, homozygotes for the eNOS T-allele (rs2070744) are 2.5 times less common in the group under consideration (18.9 vs 46.7%, respectively, p=0.019). No statistically significant difference in the frequency of occurrence of polymorphisms VEGF-A (rs2010963), HIF-1A (rs11549465) was found in the intergroup comparison. The chances of developing AUB in obese patients with heterozygous TS genotype according to eNOS rs2070744 were 3.5 times higher than in normal-weight patients (OR=3.54; 95% CI 1.29–9.79, p<0.05).
Conclusion. The obtained results suggest the influence of obesity on angiogenesis and endometrial dysfunction and, as a consequence, the development of AUB in patients of this cohort. For more accurate confirmation, it is necessary to search for immunohistochemical markers of angiogenesis and hypoxia in endometrial tissue, which will allow us to develop a prognostic model of AUB in obese patients and timely prevent possible risks of developing this disease.
Keywords:abnormal uterine bleeding; obesity; genetic polymorphisms; VEGF-A; HIF-1A; eNOS
Funding. This publication has been supported by project N 030145-0-000.
Conflict of interest. The authors declare no conflict of interest.
Contribution. Concept and design of the study – Khamoshina M.B., Azova М.М.; literature review – Artemenko Yu.S.; collection and processing of materials – Artemenko Yu.S., Tskhovrebova L.V., Petrovskaya S.A.; statistical data processing – Artemenko Yu.S., Aghajanyan A.V.; text writing – Artemenko Yu.S., Tskhovrebova L.V. All the authors made a significant contribution to the development of the concept, research and preparation of the article, read and approved the final version before publication.
For citation: Khamoshina M.B., Artemenko Yu.S., Azova M.M., Tskhovrebova L.V., Aghajanyan A.V., Petrovskaya S.A. Abnormal uterine bleeding in obese patients and polymorphisms of the eNOS, VEGF-A and HIF-1A genes. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2023; 11 (3): 5–11. DOI: https://doi.org/10.33029/2303-9698-2023-11-3-5-11 (in Russian)
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