On molecular genetic predictors of preeclampsia

Syundyukova E.G.; Chulkov V.S.; Medvedev B.I.; Naimushina Yu.V.; Ryabikina M.G.

doi:https://doi.org/10.17116/rosakush20242406126

Syundyukova E.G.

South Ural State Medical University;
Clinic of the South Ural State Medical University

ORCID: 0000-0001-9535-1871

Chulkov V.S.

Yaroslav the Wise Novgorod State University

ORCID: 0000-0002-0952-6856

Medvedev B.I.

South Ural State Medical University;
Clinic of the South Ural State Medical University

Naimushina Yu.V.

South Ural State Medical University

ORCID: 0000-0002-6032-3501

Ryabikina M.G.

South Ural State Medical University;
Clinic of the South Ural State Medical University

ORCID: 0000-0003-0943-0448

On molecular genetic predictors of preeclampsia

Authors:

Syundyukova E.G., Chulkov V.S., Medvedev B.I., Naimushina Yu.V., Ryabikina M.G.

More about the authors

Journal: Russian Bulletin of Obstetrician-Gynecologist. 2024;24(6): 26‑34

DOI: 10.17116/rosakush20242406126

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To cite this article:

Syundyukova EG, Chulkov VS, Medvedev BI, Naimushina YuV, Ryabikina MG. On molecular genetic predictors of preeclampsia. Russian Bulletin of Obstetrician-Gynecologist. 2024;24(6):26‑34. (In Russ.)
https://doi.org/10.17116/rosakush20242406126

Подписка 2026 Российский вестник акушера-гинеколога (Russian Bulletin of Obstetrician-Gynecologist)

Использование инфографики авторами научных работ

OBJECTIVE

To study the molecular genetic characteristics of pregnant women with preeclampsia, to identify probable predictors of this pathology.

MATERIAL AND METHODS

A prospective cohort study was conducted using the continuous sam-pling method: 29 pregnant women without preeclampsia, 66 with preeclampsia (32 observations of moderate preeclampsia and 34 observations of severe preeclampsia). The anamnesis of pa-tients, pregnancy outcomes, polymorphisms of genes of hemostasis (FII, FV, FVII, F13, FGB, ITGA2, ITGB3, PAI-1), renin-angiotensin-aldosterone system (AGT, AGTR1, AGTR2, CYP11B2), nitric oxide metabolism (NOS3), angiogenesis (VEGFA), adducin-1-alpha (ADD1), G-protein beta-3 (GNB) were studied. Statistical methods (SPSS Statistica for Windows 17.0): Pearson chi-square test, odds ratio (OR) with 95% confidence interval (CI), multivariate dimen-sionality reduction (MDR), and multiple logistic regression (p<0.05) were used.

RESULTS

The frequency of diagnosis of the 4G allele (79%) rs1799889 of the PAI-1 gene (OR 4.17; 95% CI 1.52—11.1; p<0.001), the A allele (72.6%) rs1403543 of the AGTR2 gene (OR 2.44; 95% CI 0.93-6.25; p=0.003) in women with preeclampsia was higher than in the control group. The C/C genotype of rs2010963 of the VEGFA gene was more common in severe preeclampsia (21.9% versus 4%; p=0.039). In the control group, a statistically significant increase in the fre-quency of the T allele of rs1799998 of the CYP11B2 gene (88% versus 75.8%; OR 0.54; 95% CI 0.22—1.33; p=0.007) and the T allele of rs4961 of the ADD1 gene (60% versus 43.5%; OR 0.52; 95% CI 0.2—1.32; p=0.03) was noted. Based on the MDR results, “Cluster 1” was formed: VEG-FA G(–634) C, ITGB3 T1565C (pronounced synergism was registered); «Cluster 2» — PAI-1 5G(–675)4G, AGTR1 A1166C (characterized by pronounced antagonism), CYP11B2 C(-344)T. The pairs of alleles 4G rs1799889 of the PAI-1 gene/T rs1799998 of the CYP11B2 gene and 4G rs1799889 of the PAI-1 gene/C rs5186 of the AGTR1 gene were associated with an increased likelihood of developing preeclampsia. A prognostic model of preeclampsia was proposed, the specificity of which was 84%, sensitivity — 95.2%, accuracy — 92%.

CONCLUSION

The use of molecular genetic technologies allows timely identification of pregnant women at high risk of developing preeclampsia and ensure its early prevention.

Keywords:

preeclampsia

predictors

gene polymorphisms

Authors:

Syundyukova E.G.

South Ural State Medical University;
Clinic of the South Ural State Medical University

ORCID: 0000-0001-9535-1871

Chulkov V.S.

Yaroslav the Wise Novgorod State University

ORCID: 0000-0002-0952-6856

Medvedev B.I.

South Ural State Medical University;
Clinic of the South Ural State Medical University

Naimushina Yu.V.

South Ural State Medical University

ORCID: 0000-0002-6032-3501

Ryabikina M.G.

South Ural State Medical University;
Clinic of the South Ural State Medical University

ORCID: 0000-0003-0943-0448

Received:

16.01.2024

Accepted:

19.02.2024

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References:

Robillard PY, Dekker G, Scioscia M, Bonsante F, Boukerrou M, Iacobelli S, Tran PL. Preeclampsia in 2023: Time for preventing early onset- and term preeclampsia: The paramount role of gestational weight gain. J Reprod Immunol. 2023;158:103968. https://doi.org/10.1016/j.jri.2023.103968
Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, Gotsch F, Erez O. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226:2S:S844—S866. https://doi.org/10.1016/j.ajog.2021.11.1356
Dolgushina VF, Syundyukova EG, Chulkov VS, Ryabikina MG. Long-term outcomes of hypertensive disorders of pregnancy. Akusherstvo i ginekologiya. 2021;10:14-20. (In Russ.). https://doi.org/10.18565/aig.2021.10.14-20
Benschop L, Duvekot JJ, Versmissen J, van Broekhoven V, Steegers EAP Roeters van Lennep J. Blood pressure profile 1 year after severe preeclampsia. Hypertension. 2018;71:3:491-498. https://doi.org/10.1161/HYPERTENSIONAHA.117.10338
Riise HKR, Sulo G, Tell GS, Igland J, Egeland G, Nygard O, Selmer R, Iversen AC, Daltveit AK. Hypertensive pregnancy disorders increase the risk of maternal cardiovascular disease after adjustment for cardiovascular risk factors. Int J Cardiol. 2019;282:81-87. https://doi.org/10.1016/j.ijcard.2019.01.097
Abramova MYu, Churnosov MI. Genetic studies of pre-eclampsia. Russian Bulletin of Obstetrician-Gynecologist. 2022;22:6:27-34. (In Russ.). https://doi.org/10.17116/rosakush20222206127
Syundyukova EG, Chulkov VS, Ryabikina MG. Preeclampsia: The Modern state of the problem. Doctor.Ru. 2021;20:1:11-16. (In Russ.). https://doi.org/10.18565/aig.2021.10.14-20
Wang X, Sun T, Chen G, Gao H. Association between vascular endothelial growth factor gene polymorphisms and pre-eclampsia susceptibility: An Updated meta-analysis. Immunol Invest. 2020;49: 1-2:120-133. https://doi.org/10.1080/08820139.2019.1659812
Loskutova T, Donskay Y, Petulko A, Kryachkova N. Risk of placenta-associated complications at preeclampsia in pregnant women with thrombophilia. Wiad Lek. 2022;75:12:2969-2973. https://doi.org/10.36740/WLek202212113
Rokotyanskaya EA, Panova IA, Malyshkina AI, Fetisova IN, Fetisov NS, Kharlamova NV, Kuligina MV. Technologies for prediction of preeclampsia. Sovrem Tekhnologii Med. 2021;12:5:78-84. https://doi.org/10.17691/stm2020.12.5.09
Dolgushina VF, Chulkov VS, Vereina NK, Sinitsyn SP. Assessing the relationship of clinical and genetic factors to pregnancy complications and outcomes in women with preeclampsia in the presence of chronic hypertension. Russian Bulletin of Obstetrician-Gynecologist. 2014;14:6:4-8. (In Russ.).
Zeng R, Jiang R, Huang W, Wang J, Zhang L, Ma Y, Wu Y, Meng M, Lan H, Lian Q, Leung FW, Sha W, Chen H. Dissecting shared genetic architecture between obesity and multiple sclerosis. EBioMedicine. 2023;93:104647. https://doi.org/10.1016/j.ebiom.2023.104647
van Oort S, Beulens JWJ, van Ballegooijen AJ, Grobbee DE, Larsson SC. Association of cardiovascular risk factors and lifestyle behaviors with hypertension: A Mendelian randomization study. Hypertension. 2020;76:6:1971-1979. https://doi.org/10.1161/HYPERTENSIONAHA.120.15761
Ponomarenko IV. Using the method of Multifactor Dimensionality Reduction (MDR) and its modifications for analysis of gene-gene and gene-environmentinteractions in genetic-epidemiological studies (review). Nauchnye resul’taty biomeditsinskikh issledovanii. 2019;5:1:4-21. (In Russ.). https://doi.org/10.18413/2313-8955-2019-5-1-0-1
Milenkovic J, Milojkovic M, Mitic D, Stoimenov TJ, Smelcerovic Z, Stojanovic D, Vujic S, Bojanic N. Interaction of thrombophilic SNPs in patients with unexplained infertility-multifactor dimensionality reduction (MDR) model analysis. J Assist Reprod Genet. 2020;37:6:1449-1458. https://doi.org/10.1007/s10815-020-01808-4
Maksimov IB, Stolyar VP, Bogomolov AV. Applied theory of information support for biomedical research. Binom. 2013;312. (In Russ.).
Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240:1285-1293. https://doi.org/10.1126/science.3287615
Skeith L, Blondon M, Ní Áinle F. Understanding and preventing placenta-mediated pregnancy complications. Hamostaseologie. 2020;40:3:356-363. https://doi.org/10.1055/a-1184-8388
Giannakou K, Evangelou E, Papatheodorou SI. Genetic and non-genetic risk factors for pre-eclampsia: Umbrella review of systematic reviews and meta-analyses of observational studies. Ultrasound Obstet Gynecol. 2018;51:720-730. https://doi.org/10.1002/uog.18959
Spiezia L, Campello E, Valle FD, Woodhams B, Simioni P. Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation. Clin Chem Lab Med. 2017;55:4:484-488. https://doi.org/10.1515/cclm-2016-0399
Frolova NI, Belokrinitskaya TE, Kolmakova KA. Molecular markers and epigenetic risk factors of preeclampsia in the era of predictive medicine. Voprosy ginekologii, akusherstva i perinatologii. 2019;18:4:95-103. (In Russ.). https://doi.org/10.20953/1726-1678-2019-4-95-103
Guo X, Yi H, Li TC, Wang Y, Wang H, Chen X. Role of vascular endothelial growth factor (VEGF) in human embryo implantation: Clinical implications. Biomolecules. 2021;11:2:253. https://doi.org/10.3390/biom11020253
Keshavarzi F, Shahrakipoor M, Teimoori B, Yaghmaei M, Narooei-Nejad M, Rasooli A, Salimi S. Association of the placental VEGF promoter polymorphisms and VEGF mRNA expression with preeclampsia. Clin Exp Hypertens. 2019;41:3:274-279. https://doi.org/10.1080/10641963.2018.1469644
Ding G, Li Y, Gao J, Wang W, Wang H, Bai G. Associations between AGT, MTHFR, and VEGF gene polymorphisms and preeclampsia in the Chinese population. Placenta. 2022;118:38-45. https://doi.org/10.1016/j.placenta.2022.01.004
Belokrinitskaya TE, Frolova NI, Strambovskaya NN, Kolmakova KA. Prevalence and intergenic interactions of polymorphisms associated with arterial hypertension, endothelial dysfunction, hemostasis and folate metabolism disorders in severe preeclampsia. ENI Zabaikal’skii meditsinskii vestnik. 2019;1:1-13. (In Russ.). https://zabmedvestnik.ru/journal/2019/1/1.pdf
Hong K, Kim SH, Cha DH, Park HJ. Defective uteroplacental vascular remodeling in preeclampsia: Key molecular factors leading to long term cardiovascular disease. Int J Mol Sci. 2021;22:11202. https://doi.org/10.3390/ijms222011202
Zhang JR, Hu WN, Li CY. A Review of the epidemiological evidence for adducin family gene polymorphisms and hypertension. Cardiol Res Pract. 2019;2019:7135604. https://doi.org/10.1155/2019/7135604
Azimi-Nezhad M, Teymoori A, Ebrahimzadeh-Vesal R. Association of CYP11B2 gene polymorphism with preeclampsia in north east of Iran (Khorasan province). Gene. 2020;733:144358. https://doi.org/10.1016/j.gene.2020.144358
Wang X, Kong Y, Chen X, Weng Z, Li B. Pertinence between risk of preeclampsia and the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms: An Updated meta-analysis based on 73 studies. J Obstet Gynaecol. 2023;43:1:2171782. https://doi.org/10.1080/01443615.2023.2171782