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

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Abstract


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.


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About the authors

Larisa D. Belotserkovtseva

Surgut State University

Email: mar-mariot@yandex.ru
SPIN-code: 2555-8470

Russian Federation, Surgut

MD, PhD, DSci (Medicine), Professor, Honored Doctor of the Russian Federation, Head of the Department of Obstetrics, Gynecology and Perinatology

Lyudmila V. Kovalenko

Surgut State University

Email: lvkhome@yandex.ru
ORCID iD: 0000-0001-5708-7328
SPIN-code: 7543-8016

Russian Federation, Surgut

The Doctor of Medical Science, Professor, Head of the  Pathophysiology and General Pathology Department

Angelika E. Kasparova

Surgut State University

Email: anzkasparova@yandex.ru
SPIN-code: 7139-3486

Russian Federation, Surgut

MD, PhD, DSci (Medicine), Professor. The Department of Pathophysiology and General Pathology, Medical Institute

Inna I. Mordovina

Surgut State University

Author for correspondence.
Email: mar-mariot@yandex.ru
ORCID iD: 0000-0003-4415-7897

Russian Federation, Surgut

MD, PhD, Associate Professor. The Department of Obstetrics, Gynecology and Perinatology, Medical Institute

Maxim Yu. Donnikov

Surgut State University

Email: donnikov@gmail.com

Russian Federation, Surgut

Researcher. The Scientific and Educational Center, Medical Institute

Denis P. Telitsyn

Surgut State University

Email: telicyndenis@gmail.com

Russian Federation, Surgut

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

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Supplementary files

Supplementary Files Action
1.
Fig. 1. Intergenic interactions of polymorphic loci of genes involved in hemostasis system and the folate cycle in preeclampsia. Strong synergy (light gray), moderate synergy (dark gray), additive interaction (black); interaction strength and direction is expressed in entropy, %

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2.
Fig. 2. Intergenic interactions of polymorphic loci of genes involved in hemostasis system and the folate cycle in healthy patients. Strong synergy (light gray), moderate synergy (dark gray), additive interaction (black); interaction strength and direction is expressed in entropy, %

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Copyright (c) 2020 Belotserkovtseva L.D., Kovalenko L.V., Kasparova A.E., Mordovina I.I., Donnikov M.Y., Telitsyn D.P.

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