Polymorphic loci of the ESR1 gene are associated with the risk of developing preeclampsia with fetal growth retardation
Abstract
Aim: to analyze the association of the ESR1 gene polymorphic loci rs2234693, rs9340799, and rs3798577 with developing preeclampsia (PE) with fetal growth retardation (FGR).
Materials and Methods. The study was performed while analyzing a sample of 400 women: 76 pregnant women with PE and FGR and 324 with a physiological course of pregnancy. Three polymorphic loci of the ESR1 gene (rs2234693, rs9340799, and rs3798577) were genotyped. Functional effects of polymorphic loci were evaluated by using the online programs HaploReg (epigenetic effects) and GTEx Portal (relation to gene expression).
Results. The development of PE and FGR is associated with the G allele and GG genotype rs9340799 of the ESR1 gene (OR = 1.38; pperm = 0.04 and OR = 2.00; pperm = 0.04, respectively), the T allele rs3798577 of the ESR1 gene (OR = 1.46; pperm = 0.01), and the TG haplotype of the polymorphic loci rs2234693–rs9340799 of the ESR1 gene (OR = 2.08; pperm = 0.009). Polymorphic locirs2234693, rs9340799 ESR1 gene and rs3798577 have an important functional significance in human body being located in the evolutionarily conserved DNA region, affect affinity of regulatory DNA motifs to the eight transcription factors as well as ESR1 gene expression in the thyroid gland, which are positioned in the promoter and enhancer region, DNAse 1 hypersensitivity motif within diverse organs and tissues, and display an important pathogenetic effect for development of PE and FGR.
Conclusion. Polymorphic loci rs2234693, rs9340799 and rs3798577 of the ESR1 gene are associated with developing PE and FGR.
About the Authors
O. V. Golovchenko
Belgorod State National Research University
Russian Federation
Russian Federation
Oleg V. Golovchenko – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Medical Institute
85 Pobedy Str., Belgorod 308007
M. Yu. Abramova
Belgorod State National Research University
Russian Federation
Russian Federation
Maria Yu. Abramova – MD, Postgraduate Student, Department of Biomedical Disciplines, Medical Institute
85 Pobedy Str., Belgorod 308007
I. V. Ponomarenko
Belgorod State National Research University
Russian Federation
Russian Federation
Irina V. Ponomarenko – MD, Dr Sci Med, Associate Professor, Department of Biomedical Disciplines
85 Pobedy Str., Belgorod 308007
M. I. Churnosov
Belgorod State National Research University
Russian Federation
Russian Federation
Mikhail I. Churnosov – MD, Dr Sci Med, Professor, Head of the Department of Biomedical Disciplines, Medical Institute
85 Pobedy Str., Belgorod 308007
References
1. Strizhakov A.M., Lipatov I.S., Tezikov Yu.V. Placental insufficiency: pathogenesis, prognosis, diagnosis, prevention, obstetric tactics. [Placentarnaya nedostatochnost': patogenez, prognozirovanie, diagnostika, profilaktika, akusherskaya taktika]. Samara: Ofort, 2014. 239 s. (In Russ.).
2. Heshmat S.H. Intrauterine growth restriction – a review article. Anatomy Physiol Biochem Int J. 2017;1(5):555–72. https://doi.org/10.19080/APBIJ.2017.01.555572.
3. Sharma D., Shastri S., Sharma P. Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr. 2016;10:67–83. https://doi.org/10.4137/CMPed.S40070.
4. Devaskar S.U., Chu A. Intrauterine growth restriction: hungry for an answer. Physiology (Bethesda). 2016;31(2):131–46. https://doi.org/10.1152/physiol.00033.2015.
5. Malhotra A., Allison B.J., Castillo-Melendez M. et al. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front Endocrinol (Lausanne). 2019;10:55. https://doi.org/10.3389/fendo.2019.00055.
6. Melkozerova O.A., Bashmakova N.V., Tretyakova T.B., Shchedrina I.D. Molecular-genetic and epigenetic aspects of impaired endometrial receptivity in women with low birth weight. [Molekulyarnogeneticheskie i epigeneticheskie aspekty narusheniya receptivnosti endometriya u zhenshchin s nizkoj massoj tela pri rozhdenii]. Voprosy ginekologii, akusherstva i perinatologii. 2019;18(4):35–43. (In Russ.). https://doi.org/10.20953/1726-1678-2019-4-35-43.
7. Yavorskaya S.D., Dolgova N.S., Fadeeva N.I., Ananina L.P. Maternal clinical and anamnestic factors for intrauterine growth restriction. [Materinskie kliniko-anamnesticheskie faktory formirovaniya zaderzhki rosta ploda]. Voprosy ginekologii, akusherstva i perinatologii. 2019;18(5):83–7. (In Russ.). https://doi.org/10.20953/1726-1678-2019-5-83-87.
8. Gusar V.A., Timofeeva A.V., Kan N.E. et al. The expression profile of placental microRNAs as regulators of oxidative stress in fetal growth restriction. [Profil' ekspressii placentarnyh mikroRNK – regulyatorov okislitel'nogo stressa pri sindrome zaderzhki rosta ploda]. Akusherstvo i ginekologiya. 2019;(1):74–80. (In Russ.). https://doi.org/10.18565/aig.2019.1.74-80.
9. Khachatryan Z.V., Kan N.E., Krasnyi A.M. et al. Gene methylation in the placenta of fetuses with fetal growth restriction. [Metilirovanie genov v placente pri zaderzhke rosta plod]. Akusherstvo i ginekologiya. 2019;(12):54–8. (In Russ.). https://doi.org/10.18565/aig.2019.12.54-58.
10. Reshetnikov E., Zarudskaya O., Polonikov A. et al. Genetic markers for inherited thrombophilia are associated with fetal growth retardation in the population of Central Russia. J Obstet Gynaecol Res. 2017;43(7):1139–44. https://doi.org/10.1111/jog.13329.
11. Malyshkina A.I., Boiko E.L., Sotnikova N.Yu. et al. Interleukin-10 production and secretion in blood in relation to interleukin-10 A-1082G polymorphism in pregnant women with fetal growth restriction. [Produkciya i sekreciya IL-10 v krovi v zavisimosti ot polimorfizma gena IL-10 A-1082G u zhenshchin s zaderzhkoj rosta ploda]. Akusherstvo i ginekologiya. 2019;(6):40–6. (In Russ.). https://doi.org/10.18565/aig.2019.6.40-46.
12. Sorokina I.N., Rudykh N.A., Bezmenova I.N., Polyakova I.S. Population genetic characteristics and genetic epidemiological research of candidate genes associations with multifactorial diseases. [Populyacionno-geneticheskie harakteristiki i genetikoepidemiologicheskoe issledovanie associacij genov-kandidatov s mul'tifaktorial'nymi zabolevaniyami]. Nauchnye rezul'taty biomedicinskih issledovanij = Research Results in Biomedicine. 2018;4(4):20–30 (In Russ.). https://doi.org/10.18413/2313-8955-2018-4-4-0-3.
13. Serebrova V.N., Trifonova E.A., Stepanov V.A. Evolutionary-genetic analysis of the role of regulatory regions in CORO2A gene in the development of hereditary predisposition to preeclampsia in Russian and Yakut ethnic groups. [Evolyucionno-geneticheskij analiz roli regulyatornyh uchastkov gena CORO2A v formirovanii nasledstvennoj predraspolozhennosti k preeklampsii u russkih i yakutov]. Nauchnye rezul'taty biomedicinskih issledovanij = Research Results in Biomedicine. 2018;4(3):38–48. (In Russ.). https://doi.org/10.18413/2313-8955-2018-4-3-0-4.
14. Ponomarenko I.V., Reshetnikov E.A., Polonikov A.V., Churnosov M.I. The polymorphic locus rs314276 of the LIN28B gene is associated with the age of menarche in women in the Central Black Earth Region of Russia. [Polimorfnyj lokus rs314276 gena LIN28B associirovan s vozrastom menarhe u zhenshchin Central'nogo Chernozem'ya Rossii]. Akusherstvo i ginekologiya. 2019;(2):98–104. (In Russ.). https://doi.org/10.18565/aig.2019.2.98-104.
15. Ponomarenko I.V., Reshetnikov E.A., Altuchova O.B. et al. Association of genetic polymorphisms with age at menarche in Russian women. Gene. 2019;686:228–36. https://doi.org/10.1016/j.gene.2018.11.042.
16. Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Polymorphic LHCGR gene loci associated with the development of uterine fibroids. [Polimorfnye lokusy gena LHCGR, associirovannye s razvitiem miomy matki]. Akusherstvo i ginekologiya. 2018;(10):86–91. (In Russ.). https://doi.org/10.18565/aig.2018.10.86-91.
17. Dovzhikova I.V., Andrievskaya I.A. Estrogen receptors (review). Part 1. [Receptory estrogenov (obzor literatury). Chast' 1]. Byulleten' fiziologii i patologii dyhaniya. 2018;(72):120–7. (In Russ.).
18. Dovzhikova I.V., Andrievskaya I.A. Estrogen receptors (review). Part 2. [Receptory estrogenov (obzor literatury). Chast' 2]. Byulleten' fiziologii i patologii dyhaniya. 2018;(73):125–33. (In Russ.).
19. Akram S.K., Sahlin L., Ostlund E. et al. Placental IGF-I, estrogen receptor, and progesterone receptor expression, and maternal anthropometry in growth-restricted pregnancies in the Swedish population. Horm Res Paediatr. 2011;75(2):131−7. https://doi.org/10.1159/000320466.
20. 20. Zhao G., Cai Y., Liu J., Meng T. Association between the estrogen receptor α gene polymorphisms rs2234693 and rs9340799 and severe and mild pre-eclampsia: a meta-analysis. Biosci Rep. 2019;39(2):BSR20181548. https://doi.org/10.1042/BSR20181548.
21. Rafnar T., Gunnarsson B., Stefansson O.A. et al. Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits. Nat Commun. 2018;9(1):3636. https://doi.org/10.1038/s41467-018-05428-6.
22. Fejerman L., Ahmadiyeh N., Hu D. et al. Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25. Nat Commun. 2014;5:5260. https://doi.org/10.1038/ncomms6260.
23. Sapkota Y., Steinthorsdottir V., Morris A.P. et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun. 2017a;8:15539. https://doi.org/10.1038/ncomms15539.
24. Krivoshei I.V., Altuchova O.B., Golovchenko O.V. et al. Genetic factors of hysteromyoma. Res J Med Sci. 2015;9 (4):182–5.
25. Välimäki N., Kuisma H., Pasanen A. et al. Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. Elife. 2018;7:e37110. https://doi.org/10.7554/eLife.37110.
26. Churnosov M.I., Altuchova O.B., Demakova N.A. et al. Associations of cytokines genetic variants with myomatous knots sizes. Res J Pharm Biol Chem Sci. 2014;5(6) 1344–7.
27. Gallagher C.S., Mäkinen N., Harris H.R. et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun. 2019;10(1):4857. https://doi.org/10.1038/s41467-019-12536-4.
28. Krivoshei I.V., Altuchova O.B., Polonikov A.V., Churnosov M.I. Bioinformatic analysis of the liability to the hyperplastic processes of the uterus. Res J Pharm Biol Chem Sci. 2015;6(5):1563–6.
29. Ponomarenko I.V., Reshetnikov E.A., Polonikov A.V. et al. The ESR1 gene polymorphism is associated with the age of menarche in Russian women. [Polimorfizm gena ESR1 associirovan s vozrastom menarhe u zhenshchin Rossii]. Voprosy ginekologii, akusherstva i perinatologii. 2019;18(5) 29–34. (In Russ.). https://doi.org/10.20953/1726-1678-2019-5-29-34.
30. Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Association of ESR2 rs4986938 polymorphism with the development of endometrial hyperplasia. [Associaciya polimorfizma rs4986938 gena ESR2 s razvitiem giperplazii endometriya]. Akusherstvo i ginekologiya. 2019;4:66–72. (In Russ.). https://doi.org/10.18565/aig.2019.4.66-72.
Review
For citations:
Golovchenko O.V., Abramova M.Yu., Ponomarenko I.V., Churnosov M.I. Polymorphic loci of the ESR1 gene are associated with the risk of developing preeclampsia with fetal growth retardation. Obstetrics, Gynecology and Reproduction. 2020;14(6):583-591. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2020.187
Views: 612
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Email this article 
