Genes predisposing to acute cerebral circulatory failure in severe pre-eclampsia in the Kazakh population

Svyatova G. Urazbayeva G. Berezina G. Terlikbayeva A. Murtazaliyeva A.
September 2025 John Wiley and Sons Ltd

International Journal of Gynecology and Obstetrics
2025 #170 Issue 3 1356 - 1372 pp.

Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

acute cerebral circulatory failure , gene polymorphisms , minor alleles , pregnancy , replicative genotyping

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Republican Medical and Genetic Consultation, JSC “Scientific Centre for Obstetrics, Gynaecology and Perinatology”, Almaty, Kazakhstan
“Center оf Molecular Medicine” LLP, Almaty, Kazakhstan
Department of Obstetrics and Gynaecology, JSC “Scientific Centre for Obstetrics, Gynaecology and Perinatology”, Almaty, Kazakhstan
Department of Strategic Development and Science, JSC “Scientific Centre for Obstetrics, Gynaecology and Perinatology”, Almaty, Kazakhstan
Department of Continuing Education, JSC “Scientific Centre for Obstetrics, Gynaecology and Perinatology”, Almaty, Kazakhstan

Republican Medical and Genetic Consultation
“Center оf Molecular Medicine” LLP
Department of Obstetrics and Gynaecology
Department of Strategic Development and Science
Department of Continuing Education

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