Preeclampsia (PE) is a severe complication of pregnancy accompanied by arterial hypertension, edema, or proteinuria with impaired functioning of various organs and systems. It is also an important medical and social problem, which has been one of the leading causes of maternal and perinatal mortality and morbidity worldwide. Despite the achievements of modern medicine, the etiology of this pathology is still unknown. Recently, many scientists have especially focused on the study of genetic factors underlying the etiopathogenesis of PE, namely, the contribution of individual polymorphic loci of various candidate genes. The current study aimed to investigate the clinical characteristics of PE and the contribution of the polymorphic loci rs1042838 of Progesterone Receptor (PGR) gene and rs8068318 of the T-Box Transcription Factor 2 (TBX2) gene to the development of PE. The study was conducted on 219 women with PE with the mean±SD age of 26.52±5.51 years and 329 women with the physiological course of pregnancy as the control group with the mean±SD age of 26.27±4.88 years. In total, 64.20%, 68.29%, 16.44%, 98.63%, and 35.48% of women with PE had increased systolic and normal diastolic blood pressure (SBP and DBP) values, proteinuria, edema, and overweight (BMI≥25), respectively. In the control group, 100%, 1.53%, 1.12%, and 35.48% of cases had normal SBP values with no proteinuria, DBP>90 mm Hg, edema, and overweight (BMI≥25), respectively. An association was observed between the CC genotype of the rs8068318 polymorphism of the TBX2 gene with the risk of developing PE in women with PE (OR=2.12, 95%CI: 1.14-3.92, P=0.02). In addition, there was an association between the rs8068318 TBX2 polymorphic locus with lower SBP (Me=140, Q25 – Q75 130 – 142.5, P=0.01) and PBP (Me=50, Q25 – Q75 40 – 55, P<0.01). According to the GeneCards database, the TBX2 gene, a member of a phylogenetically conserved gene family, is located on the long arm of chromosome 17 and encodes the TBX2 T-box transcription factor protein, which is a regulator of the transcriptional activity of various genes (i.e., it suppresses the expression of CDKN2A (p19/ARF), inhibits cyclin-dependent kinase p21 Cip1 (CDKN1A), and affects the expression of MYC, RAS, BRCA1, and BRCA2 genes). |
- WHO. WHO recommendations for the prevention and treatment of preeclampsia and eclampsia. 2014.
- Henderson JT, Thompson JH, Burda BU, Cantor A, Beil T, Whitlock EP. Screening for preeclampsia: a systematic evidence review for the US Preventive Services Task Force. 2017.
- Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42(6):1206-52.
- Al-Jameil N, Khan FA, Khan MF, Tabassum H. A brief overview of preeclampsia. J Clin Med Res. 2014;6(1):1.
- Hoedjes M, Berks D, Vogel I, Franx A, Bangma M, Darlington A-SE, et al. Postpartum depression after mild and severe preeclampsia. J Womens Health. 2011;20(10):1535-42.
- Baker AM, Klein RL, Moss KL, Haeri S, Boggess K. Maternal serum dyslipidemia occurs early in pregnancy in women with mild but not severe preeclampsia. Am J Obstet Gynecol. 2009;201(3):293. e1-. e4.
- Nørgaard SK, Vestgaard MJ, Jørgensen IL, Ásbjörnsdóttir B, Ringholm L, McIntyre HD, et al. Diastolic blood pressure is a potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes. Diabetes Res Clin Pract. 2018;138:229-37.
- Duley L, editor The global impact of pre-eclampsia and eclampsia. Seminars in perinatology; 2009: Elsevier.
- Smith JM, Lowe RF, Fullerton J, Currie SM, Harris L, Felker-Kantor E. An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management. BMC Pregnancy Childbirth. 2013;13(1):1-11.
- Yue C-Y, Zhang C-Y, Ying C-M. Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case–control study in China. Clinica Chimica Acta. 2020;511:278-81.
- Huang T, Bedford HM, Rashid S, Rasasakaram E, Priston M, Mak-Tam E, et al. Modified Multiple Marker Aneuploidy Screening as a Primary Screening Test for Preeclampsia. 2021.
- Yarosh S, Kokhtenko E, Churnosov M, Solodilova M, Polonikov A. Joint effect of glutathione S‐transferase genotypes and cigarette smoking on idiopathic male infertility. Andrologia. 2015;47(9):980-6.
- Krivoshei I, Altuchova O, Golovchenko O, Orlova V, Churnosov M. Genetic factors of hysteromyoma. 2015.
- Filipek A, Jurewicz E. Preeklampsja â choroba kobiet w ciąży. Postępy Biochemii. 2018;64(4):232-29.
- Reshetnikov E, Zarudskaya O, Polonikov A, Bushueva O, Orlova V, Krikun E, 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.
- Reshetnikov EA, Akulova LY, Dobrodomova IS, Dvornyk VY, Polonikov AV, Churnosov MI. The insertion-deletion polymorphism of the ACE gene is associated with increased blood pressure in women at the end of pregnancy. Renin Angiotensin Aldosterone Syst. 2015;16(3):623-32.
- Fishel Bartal M, Lindheimer M, Sibai B. Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance. Am J Obstet Gynecol. 2020;10.
- Golovchenko O. Molecular genetic determinants of pre-eclampsia. Res Results Biomed. 2019;5(4):139-49.
- Pretscher J, Ruebner M, Ekici AB, Rödl M, Huebner H, Schwitulla J, et al. Genetic variations in estrogen and progesterone pathway genes in preeclampsia patients and controls in Bavaria. Arch Gynecol Obstet. 2021;303(4):897-904.
- Golovchenko O, Abramova M, Ponomarenko I, Reshetnikov E, Aristova I, Polonikov A, et al. Functionally significant polymorphisms of ESR1and PGR and risk of intrauterine growth restriction in population of Central Russia. Eur J Obstet Gynecol Reprod Biol. 2020;253:52-7.
- Chambers JC, Zhang W, Lord GM, Van Der Harst P, Lawlor DA, Sehmi JS, et al. Genetic loci influencing kidney function and chronic kidney disease. Nat Genet. 2010;42(5):373-5.
- Ponomarenko I, Reshetnikov E, Polonikov A, Churnosov M. The polymorphic locus rs314276 of the LIN28B gene is associated with the age of menarche in women of the Central Black Earth Region of Russia. Obstet Gynecol. 2019;2:98-104.
- Ponomarenko I, Polonikov A, Churnosov M. Polymorphic LHCGR gene loci associated with the development of uterine fibroids. Obstet Gynecol. 2018;10:86-91.
- Reshetnikov E, Ponomarenko I, Golovchenko O, Sorokina I, Batlutskaya I, Yakunchenko T, et al. The VNTR polymorphism of the endothelial nitric oxide synthase gene and blood pressure in women at the end of pregnancy. Taiwan J Obstet Gynecol. 2019;58(3):390-5.
- Bilican B, Goding CR. Cell cycle regulation of the T-box transcription factor tbx2. Exp Cell Res. 2006;312(12):2358-66.
|