Markers for fetal growth restriction based on the study of the polymorphism of gene regulatory regions
Gasymova Sh.R., Tyutyunnik V.L., Kan N.E., Donnikov A.E., Borisova A.G.
Objective: To study variants of gene regulatory regions and identify potential markers of fetal growth restriction.
Materials and methods: This study involved the genetic analysis of polymorphic loci of genes associated with thrombophilia, prothrombotic states, folate cycle enzyme disorders, matrix metalloproteinases and their tissue inhibitors, interleukin-1 and-10, as well as laminin and estrogen receptor genes (F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1, MTHFR, MTR, MTRR, MMP9, MMP2, TIMP2, TIMP3, IL10, IL1B, LAMC1, and ESR1) in 110 pregnant women with fetal growth restriction and 272 control patients (without fetal growth restriction). Polymerase chain reaction was used to genotype single nucleotide polymorphisms. The functional effects of polymorphic loci were assessed using HaploReg (for epigenetic effects) and GTEx Portal (for association with gene expression) software.
Results: In the group with fetal growth restriction, the T allele of the polymorphic locus -1296 C>T [rs5749511] of TIMP3 was found to be significantly associated (OR=3.14 (95% CI 1.08–9.13), p=0.03), as was the G allele of the polymorphic locus MTR: 2756 A>G (Asp919Gly) (OR=2.18 (95% CI 1.15–4.13), p=0.02) compared to the control group. A rare allele of the F7 polymorphic locus, 10976 G>A (Arg353Gln), was found to be protective against the development of fetal growth restriction (OR=0.46 (95% CI 0.21–1.01), p=0.05). In the group with fetal growth restriction, accumulation of the rare G allele of the MTRR polymorphic locus: 66 A>G (Ile22Met) was observed; however, the differences with the control group did not reach statistical significance. A statistically significant association was found between the 4G variant of the -675 5G>4G polymorphic locus of the SERPINE1 (PAI-1) gene and early onset fetal growth restriction.
Conclusion: The results of this study suggest that polymorphisms in the regulatory regions of TIMP3, MTR, MTRR, and PAI-1 can be considered potential markers of the risk of fetal growth restriction.
Authors' contributions: Gasymova Sh.R., Tyutyunnik V.L., Kan N.E., Donnikov A.E., Borisova A.G. – conception and design of the study, acquisition of data for analysis, collecting publications, material processing and analysis, statistical analysis, drafting and editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Gasymova Sh.R., Tyutyunnik V.L., Kan N.E., Donnikov A.E., Borisova A.G.
Markers for fetal growth restriction based on the study of the polymorphism of gene regulatory regions.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (11): 76-82 (in Russian)
https://dx.doi.org/10.18565/aig.2024.162
Keywords
fetal growth restriction
gene variants
single-nucleotide polymorphism
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Received 10.07.2024
Accepted 18.10.2024
About the Authors
Shagane R. Gasymova, Junior Researcher at the Department of Fetal Medicine, Institute of Obstetrics; Diagnostic Medical Sonographer at the Department of Ultrasound and Functional Diagnostics, Obstetrician-Gynecologist, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology,Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(916)542-22-99, shagane2501@mail.ru, https://orcid.org/0009-0001-2626-6670
Victor L. Tyutyunnik, Professor, Dr. Med. Sci., Leading Researcher at the Center for Scientific and Clinical Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, tioutiounnik@mail.ru,
Researcher ID: B-2364-2015, SPIN-code: 1963-1359, Authors ID: 213217, Scopus Author ID: 56190621500, https://orcid.org/0000-0002-5830-5099
Natalia E. Kan, Professor, Dr. Med. Sci., Deputy Director for Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, kan-med@mail.ru, Researcher ID: B-2370-2015, SPIN-code: 5378-8437,
Authors ID: 624900, Scopus Author ID: 57008835600, https://orcid.org/0000-0001-5087-5946
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, donnikov@dna-technology.ru, https://orcid.org/0000-0003-504-2406
Anastasia G. Borisova, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, vvv92@list.ru, https://orcid.org/0009-0004-5234-1584
Corresponding author: Shagane R. Gasymova, shagane2501@mail.ru
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