👤 Gulnara Svyatova

The aim of this study was to determine the association of immune response and lipid metabolism genes with the development of pre-eclampsia and related acute cerebral circulatory disorders in Kazakh women. Minor allele frequencies of immune response and lipid metabolism genes were determined in 1,800 healthy participants stored in the Miras Biobank of the Scientific Centre of Obstetrics, Gynaecology, and Perinatology Joint Stock Company. The main results of the study showed that TLR4 (rs4986790), PLEKHA1 (rs2281673), PLEKHG1 (rs9478812), APOE (rs7412), FTO (rs1421085) and LPL (rs285) genes were in genetic equilibrium (p > 0.05), indicating that the sample was representative and there were no significant evolutionary pressures on the studied genes. The frequencies of minor alleles in the studied sample of Kazakhs were: TLR4 - 3.3%, PLEKHA1 - 5.9%, PLEKHG1 - 27.0%, APOE - 7.8%, FTO - 28.3% and LPL - 36.0%. The obtained data can be used for further genetic studies, as well as for the development of individualised strategies for the prevention and treatment of pre-eclampsia and related complications. The identified genetic markers may help in early detection of women at increased risk of developing these conditions, which will contribute to improving clinical outcomes and reducing maternal and perinatal mortality. Show less

The Objective of the Study Was to Explore the Associations between 20 Polymorphic Loci Related to Angiogenesis, Endothelial Dysfunction, Coagulation, Fibrinolysis, Lipid Metabolism, and Immune Response. These Loci Included Genes Such as PGF (rs12411), FLT1 (rs4769612), KDR (rs2071559), ACE (rs4340), FV (rs6025), FII (rs1799963), FVII (rs6046), SERPINE1 (rs1799889), ITGA2 (rs1126643), THBD (rs1042580), FTO (rs1421085), LPL (rs285), TLR4 (rs4986790), PLEKHA1 (rs2281673), PLEKHG1 (rs9478812), and Genome-Wide Association Studies (GWAS)-Associated Genes with Pre-Eclampsia (PE; MECOM, rs419076) in the Kazakh Population. The Study Aimed to Identify their Potential Role in the Development of PE and Related Complications. A case-control genetic study was conducted with 103 Kazakh female patients with acute cerebral circulatory failure in severe PE (40 [38.8%] of whom had a fatal outcome) and 104 Kazakh female patients with severe PE from the comparison group. Genotyping of polymorphism × loci was performed by real-time polymerase chain reaction. Associations of genotypes of single nucleotide polymorphisms (SNPs) with the development of acute cerebral circulatory failure (ACF) were studied using logistic regression analysis (PLINK 1.9 beta software), both unadjusted and adjusted for potential confounders. Multiple comparisons were accounted for using the Bonferroni correction. Significant associations (P < 0.05) between genotypes (heterozygote and/or unfavorable homozygote) of five polymorphisms of coagulation genes and the odds of ACF in severe PE were found-FV: GA (odds ratio [OR] 8.10, 95% confidence interval [CI] 3.01-21.98); FII: GA (OR 3.50, 95% CI 1.80-6.78); angiogenesis and endothelial dysfunction, PGF: TT (OR 8.40, 95% CI 2.83-25.20); immune response, TLR4: AG (OR 6.70, 95% CI 1.47-30.86); and PLEKHA1: TA (OR 3.90, 95% CI 1.64-9.00). The identified genetic associations can aid in predicting the development and severity of the clinical course of ACF in severe PE, forming high-risk groups, preventing its development, and personalizing therapy for the prevention of diseases in pregnant women and the fetus. Show less

The loss of two or more pregnancies is considered recurrent miscarriage (RM). One of the causes of this pathology is the occurrence of mutations both in pleiotropic and pathway-specific regulators and in structural genes. The simplest type of such mutations is single nucleotide polymorphisms. The aim of the study is to study the relationship between gene polymorphisms of anti- and pro-inflammatory cytokines - interferon-gamma (T874A), interleukin (IL1B) (C3954T), IL6 (G572C) and IL10 (G1082A); placental function, apoptosis and angiogenesis - apolipoprotein C-III (APOC3) (G5163C), kinase insert domain receptor (A1719T, G1192A), P53 (Arg72Pro) and signal transducer and activator of transcription 3 (STAT3) (C1697G) with the development of idiopathic RM (iRM) in the Kazakh population. This was a case-control study. Molecular genetic studies were performed by TaqMan using a single site-specific amplification and real-time genotyping method in 302 women with iRM and 300 with normal reproduction. DNA isolation from the biomaterial was carried out using kits containing binding magnetic particles. Both samples were analysed for alleles and genotypes for the studied polymorphisms. For statistical data processing, Pearson's criterion, confidence interval (CI) and probability value were taken into account. It was found that the carriage of unfavourable genotypes (G/C, C/C) for the G5163C polymorphism of the APOC3 gene increases the risk of developing iRM by three times (odds ratio = 3.0; 95% CI = 2.24-4.07). Other studied polymorphisms in the genes of ILs, interferon, P53 proapoptotic protein, kinase domain receptor and STAT3 transcription activator were not associated with RM. Significant associations of APOC3 gene genotypes with the development of iRM in the Kazakh population indicate the involvement of the placental system, which is realised by vascularisation defects and defective embryo implantation and leads to early pregnancy termination. Show less