Gestational diabetes is an important interdisciplinary problem that not only obstetrician-gynecologists face, but also doctors of related specialties. Each year, the number of live births affected by hyperglycemia remains high. The steady increase in the number of complicated pregnancy and childbirth in patients with gestational diabetes, as well as long-term adverse consequences for the mother, stimulates the search for new diagnostic criteria in order to improve maternal and perinatal outcomes. The development of genetic engineering makes it possible to study the molecular basis of GSD. Objective — analysis of intergenic interactions in the formation of hereditary predisposition to gestational diabetes. Material and methods. The study was conducted on the basis of the FSBI «Research Institute OMM» Ministry of Health of the Russian Federation. 122 women recruited. Patients were divided into two groups. The main group consisted of women whose pregnancy was complicated by HSD (n=87), the control group is conditionally healthy patients (n=35). The women studied met the inclusion and exclusion criteria, which carried out a molecular genetic study by the method of pyrosequencing using the genetic analysis system of the PyroMark Q24 series. The study studied 4 polymorphic variants of loci in the genes KCNJ11 (K23E C>T), PPARG (P12A C>G), TCF7L2 (IVS3 C>T), TCF7L2 (IVS4 G>T), as well as the analysis of intergenic interactions. Results. The obtained results revealed differences in the frequency of occurrence of variant genotypes and alleles of 4m polymorphic variants of 3x studied genes in the group of women with HSD, which is significantly more frequent. This may indicate the association of genes (KCNJ11, PPARG, TCF7L2) with the risk of formation of GSD. Assessment of the complex contribution of genetic factors to the risk of formation of HPS was carried out by reducing the multivariate dimension of MDR. 7 high-risk genotypes and 15 low-risk genotypes of formation of HSD were obtained. As a result, a 3x locus model was treated, including a combination of 3 polymorphic variants in the genotype, with a sensitivity of 86%. Conclusion. An association of polymorphic gene loci with the risk of diabetes has been established. A model of intergenic gene interactions of an increased risk of the formation of gestational diabetes has been obtained. It is shown that a comprehensive assessment of various groups of polymorphisms that affect the pathogenesis of GDM is more promising in assessing the individual risk of the disease than single-factor analysis.