Молекулярно-генетические предикторы перинатальных осложнений гестационного сахарного диабета у беременных после применения вспомогательных репродуктивных технологий

Abstract

Aim: to assess the impact of carrying polymorphisms of genes related to lipid and carbohydrate metabolism, vascular tone, and angiogenesis on the complications development related to gestational diabetes mellitus (GDM) in patients with pregnancies resulting from the use of assisted reproductive technology (ART). Patients and Methods: a comprehensive cohort study was conducted. The main group (n=123), comprised of pregnant patients after the use of ART with GDM, was divided into 2 subgroups: 1A — pregnant women with perinatal complications (n=76); 1B — pregnant women without perinatal complications (n=47). The comparison group (n=105) included patients with pregnancies resulting from ART, without GDM. The perinatal complications analyzed in the study included preeclampsia, placental insufficiency, fetal growth retardation, and small for gestational age. Molecular genetic testing was conducted using allele-specific real-time PCR. Polymorphisms of the PPARG (Pro12Ala C>G), TCF7L2 (IVS3 C>T), ApoB Pro2739leu G>A, VEGF-A: -634 G>C, eNOS Glu298Asp G894T G>T genes were studied. Results: carrying the polymorphic Pro12Pro allele of the PPARG gene (Pro12Ala >G) was associated with an increased risk of developing GDM in patients after ART (odds ratio (OR) 2.451, 95% confidence interval (CI) 1.60–3.746, p=0.001). Conversely, the AlaP12Ala allele of the PPARG gene has a protective effect against these risks (OR 0.408, 95% CI 0.267–0.623, p=0.001). It was noted that carrying the TCF7L2 IVS3 TT genotype was associated with an increased risk of developing GDM in patients after ART (OR 3.795, 95% CI 1.482–9.720, p=0.004). Carrying the CC genotype of the VEGF-A -634 G>C gene (OR 3.607, 95% CI 1.084–5.218, p<0.05), as well as the recessive homozygous TT genotype of the eNOS 894 G>T gene (OR 2.637, 95% CI 1.033–6.374; p<0.05), was associated with an increased risk of developing perinatal complications of GDM in patients after ART. Conclusion: identifying genetic determinants of GDM associated with perinatal complications is important for determining the high-risk group at the stage of ART preparation and early pregnancy. Early identification of high-risk patients will allow for effective preventive measures before entry into the program, and for objective analysis of the clinical signs concerning the disease progression, as well as timely correction of carbohydrate metabolism disorders to improve perinatal outcomes. KEYWORDS: ART, gestational diabetes, perinatal complications, gene polymorphisms related to lipid and carbohydrate metabolism, gene polymorphisms — angiogenesis and vascular tone regulators. FOR CITATION: Melkozerova O.A., Murzin A.V., Tretyakova T.B., Deryabina E.G. Molecular-genetic predictors concerning the perinatal complications of gestational diabetes mellitus in pregnant women after assisted reproductive technologies. Russian Journal of Woman and Child Health. 2024;7(1):4–11 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-1.