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

Abstract

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.