Genetic predictors of the formation of placental insufficiency in patients with gestational diabetes mellitus without insulin requirement

Background. The pathogenesis of gestational diabetes mellitus (GDM) and placental insufficiency (PI) separately has been well studied. However, the mechanism of formation of pathology of the fetoplacental complex in women with gestational disorders of carbohydrate metabolism is not fully known, which dictates the need for its detailed study. Objective. To analyze the associations of alleles and genotypes of polymorphic variants of genes for endothelial dysfunction and carbohydrate metabolism disorders with the formation of PN in patients with GDM without insulin requirement. Material and methods. A longitudinal cohort comparative study was conducted. The study included 120 patients in the II-III trimester of pregnancy with GDM without insulin requirement, who were divided into two groups. The main group consisted of 70 women whose pregnancy was complicated by sub- and decompensated forms of PN. The comparison group included 50 pregnant women without pathology of the fetoplacental complex. A comparative analysis of the distribution of alleles and genotypes for polymorphic variants of genes was carried out: PPARG (Pro12Ala C>G), TCF7L2 (IVS3 C>T), TCF7L2 (IVS4 G>T), VEGF-A (C936T C>T), eNOS (G894T G>T), eNOS (T786C C>T). An assessment of intergenic interactions was made. Results. In our study, the polymorphic marker eNOS (G894T G>T) showed its significance. When analyzing the role of the genotype in the formation of the pathology under study, genotypes containing the variant 894T allele in the homo- and heterozygous state predominated in the main group, and in the comparison group homozygous genotypes with the 894G allele were more often detected. Analysis of the distribution of alleles of the studied genes showed that in the main group genotypes containing the variant T allele were more common, versus the comparison group, where the G allele was more common. Conclusion. The statistical significance of the eNOS (G894T G>T) polymorphism in the risk of placental insufficiency in patients with gestational diabetes mellitus was shown. Carriage of at least one variant allele 894T in the genotype increases the risk of placental insufficiency. The results obtained suggest that the T allele of the polymorphic locus of the eNOS (G894T G>T) gene is a risk allele for the formation of placental insufficiency in women with gestational diabetes mellitus without insulin requirement.