Specific interactions between genes of the hemostasis system, folate cycle and background comorbid pathology in the prognosis of preeclampsia

Larisa D. Belotserkovtseva; Белоцерковцева Лариса Дмитриевна; Lyudmila V. Kovalenko; Коваленко Людмила Васильевна; Angelika E. Kasparova; Каспарова Анжелика Эдуардовна; Inna I. Mordovina; Мордовина Инна Игоревна; Maxim Yu. Donnikov; Донников Максим Юрьевич; Denis P. Telitsyn; Телицын Денис Петрович

doi:10.17816/JOWD69549-58

Specific interactions between genes of the hemostasis system, folate cycle and background comorbid pathology in the prognosis of preeclampsia

作者: Belotserkovtseva L.D.¹, Kovalenko L.V.¹, Kasparova A.E.¹, Mordovina I.I.¹, Donnikov M.Y.¹, Telitsyn D.P.¹
隶属关系:
1. Surgut State University
期: 卷 69, 编号 5 (2020)
页面: 49-58
栏目: Original study articles
URL: https://bakhtiniada.ru/jowd/article/view/34024
DOI: https://doi.org/10.17816/JOWD69549-58
ID: 34024

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Hypothesis/aims of study. The search for early predictors of preeclampsia currently remains relevant. There is still a need to study maternal factors affecting the development of preeclampsia such as intergenic interactions in a pregnant woman with single nucleotide polymorphisms (SNPs) in genes associated with hemostasis system and folate cycle, as well as predictors. The aim of this study was to assess the role of comorbid pathology and gene polymorphism associated with the hemostasis system and folate cycle in predicting preeclampsia in a pregnant woman.

Study design, materials and methods. We examined 158 pregnant women in two study groups, including 92 women with preeclampsia and 66 healthy subjects. Somatic anamnesis of the patients was studied, with the course and outcomes of pregnancy analyzed. The carriage of SNPs in genes involved in hemostasis and the folate cycle was studied once by the method of polymerase chain reaction in real time with amplification of polymorphic loci and restriction analysis using specific endonucleases. The analysis of intergenic interactions was performed using the MDR 3.0.2 program.

Results. Seven genes involved in hemostasis and three genes involved in the folate cycle were studied. The highest entropy of the case-control status for preeclampsia is associated with the locus of coagulation factor F7 10976G>A — 9.49% and that of methylenetetrahydrofolate reductase MTHFR 677C>T (A223V) — 5.35%. The combination of loci of the tissue plasminogen activator inhibitor-1 gene SERPINE1 (PAI-1) and the platelet glycoprotein integrin 1α-2 gene ITGA2 (SERPINE1 (PAI-1) (5G>4G) + ITGA2 (807C> T)) account for 18.28%, and SERPINE1 (PAI1) (5G>4G) + MTHFR (677C>T) 14.26% of results. A three-locus synergy model SERPINE1 (PAI-1) (5G>4G) + MTHFR (677C>T) + ITGA2 (807C>T) responsible for the development of preeclampsia was obtained, which has a reproducibility of 10/10 and an accuracy of predictions of 84.3%.

Conclusion. Our data indicate a high contribution of the ITGA2, SERPINE1 (PAI-1), and MTHFR mutations combination to the prediction of preeclampsia.

关键词

intergenic interactions, single nucleotide polymorphism, markers, hemostasis, folate cycle, preeclampsia, plasminogen activator inhibitor-1 gene, alpha-2 integrin gene, methylenetetrahydrofolate reductase gene

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Post-Graduate Student. The Department of Obstetrics, Gynecology and Perinatology

俄罗斯联邦, Surgut

参考

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