<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533- 2025-11-2-0-1</article-id><article-id pub-id-type="publisher-id">3766</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Clinic-laboratory blood parameters and the contribution of renin-angiotensin system gene polymorphisms in pregnant women with preeclampsia&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Clinic-laboratory blood parameters and the contribution of renin-angiotensin system gene polymorphisms in pregnant women with preeclampsia&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Bordaeva</surname><given-names>Oksana Y.</given-names></name><name xml:lang="en"><surname>Bordaeva</surname><given-names>Oksana Y.</given-names></name></name-alternatives><email>bordaeva@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Alayasa</surname><given-names>Nadeim N.I.</given-names></name><name xml:lang="en"><surname>Alayasa</surname><given-names>Nadeim N.I.</given-names></name></name-alternatives><email>alayasa.nadeim@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Zezerova</surname><given-names>Yulia S.</given-names></name><name xml:lang="en"><surname>Zezerova</surname><given-names>Yulia S.</given-names></name></name-alternatives><email>ulya_ruban@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Milutina</surname><given-names>Natalya P.</given-names></name><name xml:lang="en"><surname>Milutina</surname><given-names>Natalya P.</given-names></name></name-alternatives><email>natmilut@rambler.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Derevyanchuk</surname><given-names>Ekaterina G.</given-names></name><name xml:lang="en"><surname>Derevyanchuk</surname><given-names>Ekaterina G.</given-names></name></name-alternatives><email>biolab2008@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Shkurat</surname><given-names>Tatiana P.</given-names></name><name xml:lang="en"><surname>Shkurat</surname><given-names>Tatiana P.</given-names></name></name-alternatives><email>tshkurat@yandex.ru</email></contrib></contrib-group><pub-date pub-type="epub"><year>2025</year></pub-date><volume>11</volume><issue>2</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2025/2/Биомедисследования_11_2-6-20.pdf" /><abstract xml:lang="ru"><p>Background: Preeclampsia (PE) is a pregnancy-related condition linked to hypertension and proteinuria. It is a major cause of maternal and perinatal mortality. The aim of the study: The aim of this study was to investigate the effect of PE on blood parameters and to assess its diagnostic significance. It also investigated the association between renin-angiotensin system gene polymorphisms and susceptibility to PE. Materials and methods: We studied 40 pregnant women aged 25 to 40 years (10 with normal pregnancy, 10 with mild PE, 10 with moderate PE, and 10 with severe PE). We measured alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, creatinine, and total protein levels in both normal and preeclamptic pregnancies. Furthermore, we genotyped 40 preeclamptic women and 60 normotensive pregnant controls for renin-angiotensin system gene polymorphisms. Multifactor dimensionality reduction (MDR) was carried out to assess the interactions among these polymorphisms. Results: The activity of ALT, AST, and ALP significantly increased in PE groups (mild, moderate, severe) compared to the control group (p=0.008-0.00001). Urea level significantly increased in severe PE (p=0.038). Creatinine levels increased significantly in moderate and severe PE (p=0.00004-0.00001), while total protein levels decreased significantly in all PE groups compared to the control group (p=0.001-0.00005). We also found that the T allele of the AGT (C521T; Thr174Met; rs4762) polymorphism was significantly associated with the risk of PE (p=0.005), and the TT genotype was also significant but not associated with increased risk of PE (p=0.034). The best MDR model was the four-factor model with a test balance accuracy of 0.546 and a maximum cross-validation consistency of 10/10 (p&amp;lt;0.0001). Conclusion: Preeclamptic pregnancies had elevated ALT, AST, ALP, serum urea, serum creatinine, and reduced total protein levels. In addition, the AGT (C521T; Thr174Met; rs4762) polymorphism was associated with PE risk. Furthermore, the four-factors MDR model was highly informative and associated with PE risk (p&amp;lt;0.0001)</p></abstract><trans-abstract xml:lang="en"><p>Background: Preeclampsia (PE) is a pregnancy-related condition linked to hypertension and proteinuria. It is a major cause of maternal and perinatal mortality. The aim of the study: The aim of this study was to investigate the effect of PE on blood parameters and to assess its diagnostic significance. It also investigated the association between renin-angiotensin system gene polymorphisms and susceptibility to PE. Materials and methods: We studied 40 pregnant women aged 25 to 40 years (10 with normal pregnancy, 10 with mild PE, 10 with moderate PE, and 10 with severe PE). We measured alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, creatinine, and total protein levels in both normal and preeclamptic pregnancies. Furthermore, we genotyped 40 preeclamptic women and 60 normotensive pregnant controls for renin-angiotensin system gene polymorphisms. Multifactor dimensionality reduction (MDR) was carried out to assess the interactions among these polymorphisms. Results: The activity of ALT, AST, and ALP significantly increased in PE groups (mild, moderate, severe) compared to the control group (p=0.008-0.00001). Urea level significantly increased in severe PE (p=0.038). Creatinine levels increased significantly in moderate and severe PE (p=0.00004-0.00001), while total protein levels decreased significantly in all PE groups compared to the control group (p=0.001-0.00005). We also found that the T allele of the AGT (C521T; Thr174Met; rs4762) polymorphism was significantly associated with the risk of PE (p=0.005), and the TT genotype was also significant but not associated with increased risk of PE (p=0.034). The best MDR model was the four-factor model with a test balance accuracy of 0.546 and a maximum cross-validation consistency of 10/10 (p&amp;lt;0.0001). Conclusion: Preeclamptic pregnancies had elevated ALT, AST, ALP, serum urea, serum creatinine, and reduced total protein levels. In addition, the AGT (C521T; Thr174Met; rs4762) polymorphism was associated with PE risk. Furthermore, the four-factors MDR model was highly informative and associated with PE risk (p&amp;lt;0.0001)</p></trans-abstract><kwd-group xml:lang="ru"><kwd>preeclampsia</kwd><kwd>aminotransferase</kwd><kwd>polymorphism</kwd><kwd>AGT</kwd><kwd>AGTR1</kwd><kwd>AGTR2</kwd></kwd-group><kwd-group xml:lang="en"><kwd>preeclampsia</kwd><kwd>aminotransferase</kwd><kwd>polymorphism</kwd><kwd>AGT</kwd><kwd>AGTR1</kwd><kwd>AGTR2</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Mendoza M, Tur H, Garcia-Manau P, et al. Cut-off values for Gaussian first-trimester screening for early-onset preeclampsia with maternal history, biochemical markers and uterine artery Doppler. Journal of Gynecology Obstetrics and Human Reproduction. 2021;50(1):101827. DOI: https://doi.org/10.1016/j.jogoh.2020.101827</mixed-citation></ref><ref id="B2"><mixed-citation>Giardini V, Rovelli R, Algeri P, et al. Placental growth factor as a predictive marker of preeclampsia&amp;ndash;PREBIO study&amp;ndash;PREeclampsia BIOchemical study. Journal of Maternal-Fetal and Neonatal Medicine. 2022;35(16):3029-35. DOI: https://doi.org/10.1080/14767058.2020.1792878</mixed-citation></ref><ref id="B3"><mixed-citation>Haram K, Mortensen JH, Myking O, et al. The role of oxidative stress, adhesion molecules and antioxidants in preeclampsia. Current Hypertension Reviews. 2019;15(2):105-112. DOI: https://doi.org/10.2174/1573402115666190119163942</mixed-citation></ref><ref id="B4"><mixed-citation>Akhmedov FK. Biochemical markers of preeclampsia development and criteria for early diagnosis. Art of Medicine. 2022;2(3):110-115. DOI: https://doi.org/10.5281/zenodo.7108074</mixed-citation></ref><ref id="B5"><mixed-citation>de Mendon&amp;ccedil;a ELSS, da Silva JVF, Mello CS, et al. Serum uric acid levels associated with biochemical parameters linked to preeclampsia severity and to adverse perinatal outcomes. Archives of Gynecology and Obstetrics. 2022;305:1453-1463. DOI: https://doi.org/10.1007/s00404-021-06313-2</mixed-citation></ref><ref id="B6"><mixed-citation>Fondjo LA, Amoah B, Annan JJ, et al. Hematobiochemical variability and predictors of new-onset and persistent postpartum preeclampsia. Scientific Reports. 2022;12:3583. DOI: https://doi.org/10.1038/s41598-022-07509-5</mixed-citation></ref><ref id="B7"><mixed-citation>Tarca AL, Taran A, Romero R, et al. Prediction of preeclampsia throughout gestation with maternal characteristics and biophysical and biochemical markers: a longitudinal study. American Journal of Obstetrics and Gynecology. 2022;226(1):126.e1-126.e22. DOI: https://doi.org/10.1016/j.ajog.2021.01.020</mixed-citation></ref><ref id="B8"><mixed-citation>Alonso-Ventura V, Li Y, Pasupuleti V, et al. Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis. Metabolism. 2020;102:154012. DOI: https://doi.org/10.1016/j.metabol.2019.154012</mixed-citation></ref><ref id="B9"><mixed-citation>Kornacki J, Wender-Ożegowska E. Utility of biochemical tests in prediction, diagnostics and clinical management of preeclampsia: a review. Archives of Medical Science. 2020;16(6):1370-1375. DOI: https://doi.org/10.5114/aoms.2020.97762</mixed-citation></ref><ref id="B10"><mixed-citation>Loftness BC, Bernstein I, McBride CA, et al. Preterm Preeclampsia Risk Modelling: Examining Hemodynamic, Biochemical, and Biophysical Markers Prior to Pregnancy. Proceedings of the 45th Annual International Conference of the IEEE Engineering in Medicine &amp;amp; Biology Society (EMBC), Sydney, Australi; 2023. DOI: https://doi.org/10.1109/EMBC40787.2023.10340404</mixed-citation></ref><ref id="B11"><mixed-citation>Mou AD, Barman Z, Hasan M, et al. Prevalence of preeclampsia and the associated risk factors among pregnant women in Bangladesh. Scientific Reports. 2021;11:21339. DOI: https://doi.org/10.1038/s41598-021-00839-w</mixed-citation></ref><ref id="B12"><mixed-citation>Wojczakowski W, Kimber-Trojnar Ż, Dziwisz F, et al. Preeclampsia and cardiovascular risk for offspring. Journal of Clinical Medicine. 2021;10(14):3154. DOI: https://doi.org/10.3390/jcm10143154</mixed-citation></ref><ref id="B13"><mixed-citation>Wisner K. Gestational hypertension and preeclampsia. MCN The American Journal of Maternal Child Nursing. 2019;44(3):170. DOI: https://doi.org/10.1097/NMC.0000000000000523</mixed-citation></ref><ref id="B14"><mixed-citation>Tesfa E, Munshea A, Nibret E, et al. Maternal serum uric acid, creatinine and blood urea levels in the prediction of preeclampsia among pregnant women attending ANC and delivery services at Bahir Dar city public hospitals, northwest Ethiopia: A case-control study. Heliyon. 2022;8(10):e11098. DOI: https://doi.org/10.1016/j.heliyon.2022.e11098</mixed-citation></ref><ref id="B15"><mixed-citation>Wallace K, Harris S, Addison A, et al. HELLP syndrome: pathophysiology and current therapies. Current Pharmaceutical Biotechnology. 2018;19(10):816-826. DOI: https://doi.org/10.2174/1389201019666180712115215</mixed-citation></ref><ref id="B16"><mixed-citation>Levey AS, Eckardt KU, Dorman NM, et al. Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney International. 2019;97(6):1117-1129. DOI: https://doi.org/10.1016/j.kint.2020.02.010</mixed-citation></ref><ref id="B17"><mixed-citation>Alese MO, Moodley J, Naicker T. Preeclampsia and HELLP syndrome, the role of the liver. Journal of Maternal-Fetal and Neonatal Medicine. 2021;34(1):117-123. DOI: https://doi.org/10.1080/14767058.2019.1572737</mixed-citation></ref><ref id="B18"><mixed-citation>Munazza B, Raza N, Naureen A, et al. Liver function tests in preeclampsia. Journal of Ayub Medical College, Abbottabad. 2011;23(4):3-5.</mixed-citation></ref><ref id="B19"><mixed-citation>Asha NS, Varghese A. Study of liver enzymes in preeclampsia. Journal of Medical Science and Clinical Research. 2017;5(1):15169-15172. DOI: https://doi.org/10.18535/jmscr/v5i1.06</mixed-citation></ref><ref id="B20"><mixed-citation>Connolly CT, Grubman O, Al-Ibraheemi Z, et al. A case of markedly elevated isolated alkaline phosphatase in the third trimester of pregnancy. Case Reports in Obstetrics and Gynecology. 2022;2022:1611304. DOI: https://doi.org/10.1155/2022/1611304</mixed-citation></ref><ref id="B21"><mixed-citation>Chen Y, Ou W, Lin D, et al. Increased uric acid, gamma-glutamyl transpeptidase and alkaline phosphatase in early-pregnancy associated with the development of gestational hypertension and preeclampsia. Frontiers in Cardiovascular Medicine. 2021;8:756140. DOI: https://doi.org/10.3389/fcvm.2021.756140</mixed-citation></ref><ref id="B22"><mixed-citation>Ekun OA, Olawumi OM, Makwe CC, et al. Biochemical assessment of renal and liver function among preeclamptics in lagos metropolis. International Journal of Reproductive Medicine. 2018;2018:1594182. DOI: https://doi.org/10.1155/2018/1594182</mixed-citation></ref><ref id="B23"><mixed-citation>Arthurs AL, Lumbers ER, Delforce SJ, et al. The role of oxygen in regulating microRNAs in control of the placental renin&amp;ndash;angiotensin system. Molecular Human Reproduction. 2019;25(4):206-217. DOI: https://doi.org/10.1093/molehr/gaz004</mixed-citation></ref><ref id="B24"><mixed-citation>Arthurs AL, Lumbers ER, Pringle KG. MicroRNA mimics that target the placental renin&amp;ndash;angiotensin system inhibit trophoblast proliferation. Molecular Human Reproduction. 2019;25(4):218-227. DOI: https://doi.org/10.1093/molehr/gaz010</mixed-citation></ref><ref id="B25"><mixed-citation>Zitouni H, Raguema N, Gannoun MB, et al. Impact of obesity on the association of active renin and plasma aldosterone concentrations, and aldosterone-to-renin ratio with preeclampsia. Pregnancy Hypertension. 2018;14:139-144. DOI: https://doi.org/10.1016/j.preghy.2018.09.007</mixed-citation></ref><ref id="B26"><mixed-citation>Delforce SJ, Lumbers ER, Morosin SK, et al. The Angiotensin II type 1 receptor mediates the effects of low oxygen on early placental angiogenesis. Placenta. 2019;75:54-61. DOI: https://doi.org/10.3389/fendo.2019.00563</mixed-citation></ref><ref id="B27"><mixed-citation>Timokhina EV, Strizhakov AN, Ignatko IV, et al. Genetic aspects of preeclampsia: The role of polymorphisms in the genes of the renin&amp;ndash;angiotensin system. Biochemistry. 2019;84:181-186. DOI: https://doi.org/10.1134/S0006297919020093</mixed-citation></ref><ref id="B28"><mixed-citation>Wang X, Kong Y, Chen X, et al. Pertinence between risk of preeclampsia and the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms: an updated meta-analysis based on 73 studies. Journal of Obstetrics and Gynaecology. 2023;43(1):2171782. DOI: https://doi.org/10.1080/01443615.2023.2171782</mixed-citation></ref><ref id="B29"><mixed-citation>Procopciuc LM, Nemeti G, Buzdugan E, et al. Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study. Pregnancy Hypertension. 2019;18:1-8. DOI: https://doi.org/10.1016/j.preghy.2019.08.006</mixed-citation></ref><ref id="B30"><mixed-citation>Ibrahim SH, Jonas MM, Taylor SA, et al. Liver diseases in the perinatal period: interactions between mother and infant. Hepatology. 2020;71(4):1474-1485. DOI: https://doi.org/10.1002/hep.31109</mixed-citation></ref><ref id="B31"><mixed-citation>Phipps EA, Thadhani R, Benzing T, et al. Preeclampsia: pathogenesis, novel diagnostics and therapies. Nature Reviews Nephrology. 2019;15(5):275-289. DOI: https://doi.org/10.1038/s41581-019-0119-6</mixed-citation></ref><ref id="B32"><mixed-citation>Dimitriadis E, Rolnik DL, Zhou W, et al. Preeclampsia. Nature Reviews Disease Primers. 2023;9:8. DOI: https://doi.org/10.1038/s41572-023-00417-6</mixed-citation></ref><ref id="B33"><mixed-citation>Kattah A. Preeclampsia and kidney disease: deciphering cause and effect. Current Hypertension Reports. 2020;22:91. DOI: https://doi.org/10.1007/s11906-020-01099-1</mixed-citation></ref><ref id="B34"><mixed-citation>Alameen A, Qassim AA, Mohammed A, et al. Evaluation of the effect of of preeclampsia on liver and renal function biomarkers level Left ventricular function in type 2 diabetics. Biochemical and Cellular Archives. 2021;21(2):4887-4891.</mixed-citation></ref><ref id="B35"><mixed-citation>Kalafat E, Thilaganathan B. Cardiovascular origins of preeclampsia. Current Opinion in Obstetrics and Gynecology. 2017;29(6):383-389. DOI: https://doi.org/10.1097/GCO.0000000000000419</mixed-citation></ref><ref id="B36"><mixed-citation>Lee SM, Park JS, Han YJ, et al. Elevated Alanine Aminotransferase in Early Pregnancy and Subsequent Development of Gestational Diabetes and Preeclampsia. Journal of Korean Medical Science. 2020;35(26):e198. DOI: https://doi.org/10.3346/jkms.2020.35.e198</mixed-citation></ref><ref id="B37"><mixed-citation>Kim WR, Flamm SL, Di Bisceglie AM, et al. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008;47(4):1363-1370. DOI: https://doi.org/10.1002/hep.22109</mixed-citation></ref><ref id="B38"><mixed-citation>Orabona R, Sciatti E, Sartori E, et al. The impact of preeclampsia on women&amp;rsquo;s health: cardiovascular long-term implications. Obstetrical and Gynecological Survey. 2020;75(11):703-709. DOI: https://doi.org/10.1097/OGX.0000000000000846</mixed-citation></ref><ref id="B39"><mixed-citation>Nirupama R, Divyashree S, Janhavi P, et al. Preeclampsia: Pathophysiology and management. Journal of Gynecology Obstetrics and Human Reproduction. 2021;50(2):101975. DOI: https://doi.org/10.1016/j.jogoh.2020.101975</mixed-citation></ref><ref id="B40"><mixed-citation>Kamel HEDH, Elboghdady AA, Youssef A. Association of Hypoproteinemia in Preeclampsia with Maternal and Perinatal Outcomes: A Prospective Analysis of High-Risk Women. Evidence Based Women&amp;#39;s Health Journal. 2020;10(3):246-253. DOI: https://doi.org/10.21608/ebwhj.2019.19209.1052</mixed-citation></ref><ref id="B41"><mixed-citation>Morikawa M, Mayama M, Saito Y, et al. Hypoproteinemia as a parameter of poor perinatal/neonatal outcomes in women with preeclampsia diagnosed as hypertension plus proteinuria. Pregnancy Hypertension. 2020;21:111-117. DOI: https://doi.org/10.1016/j.preghy.2020.05.012</mixed-citation></ref><ref id="B42"><mixed-citation>Br&amp;ouml;er S, Br&amp;ouml;er A. Amino acid homeostasis and signalling in mammalian cells and organisms. Biochemical Journal. 2017;474(12):1935-1963. DOI: https://doi.org/10.1042/BCJ20160822</mixed-citation></ref><ref id="B43"><mixed-citation>Prameswari N, Irwinda R, Wibowo N, et al. Maternal Amino Acid Status in Severe Preeclampsia: A Cross-Sectional Study. Nutrients. 2022;14(5):1019. DOI: https://doi.org/10.3390/nu14051019</mixed-citation></ref><ref id="B44"><mixed-citation>Guo F, Yuan P, Long W, et al. Alterations in the metabolic status of amino acids in newborns of preeclampsia women. Pregnancy Hypertension. 2022;27:170-172. DOI: https://doi.org/10.1016/j.preghy.2022.01.003</mixed-citation></ref><ref id="B45"><mixed-citation>Pogorelova TN, Gunko VO, Palieva NV, et al. Free amino acid imbalances in amniotic fluid in preeclampsia. Obstetrics and Gynecology. 2019;19(2):60-67. Russian. DOI: https://dx.doi.org/10.18565/aig.2019.2.60-67</mixed-citation></ref><ref id="B46"><mixed-citation>Gathiram P, Moodley J. The role of the renin-angiotensin-aldosterone system in preeclampsia: a review. Current Hypertension Reports. 2020;22:89. DOI: https://doi.org/10.1007/s11906-020-01098-2</mixed-citation></ref><ref id="B47"><mixed-citation>Haram K, Mortensen JH, Myking O, et al. Early development of the human placenta and pregnancy complications. Journal of Maternal-Fetal and Neonatal Medicine. 2020;33(20):3538-3545. DOI: https://doi.org/101080/1476705820191578745</mixed-citation></ref><ref id="B48"><mixed-citation>Gintoni I, Adamopoulou M, Yapijakis C. The angiotensin-converting enzyme insertion/deletion polymorphism as a common risk factor for major pregnancy complications. In Vivo. 2021;35(1):95-103. DOI: https://doi.org/10.21873/invivo.12236</mixed-citation></ref><ref id="B49"><mixed-citation>Junus K, Bj&amp;ouml;rk Ragnarsd&amp;oacute;ttir I, Nordl&amp;ouml;f Callbo P, et al. Elevated mid-pregnancy plasma levels of angiotensin-converting enzyme 2 in women prior to the development of preeclampsia. Scientific Reports. 2022;12(1):4109. DOI: https://doi.org/10.1038/s41598-022-08081-8</mixed-citation></ref><ref id="B50"><mixed-citation>Lea&amp;ntilde;os-Miranda A, Campos-Galicia I, M&amp;eacute;ndez-Aguilar F, et al. Lower circulating angiotensin II levels are related to the severity of preeclampsia and its risk as disclosed by a specific bioassay. Medicine. 2018;97(39):e12498. DOI: https://doi.org/10.1097/MD.0000000000012498</mixed-citation></ref><ref id="B51"><mixed-citation>Lu HQ, Hu R. The role of immunity in the pathogenesis and development of pre‐eclampsia. Scandinavian Journal of Immunology. 2019;90(5):e12756. DOI: https://doi.org/10.1111/sji.12756</mixed-citation></ref><ref id="B52"><mixed-citation>Morgan T, Craven C, Lalouel JM, et al. Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spiral arteries in first-trimester decidua. American Journal of Obstetrics and Gynecology. 1999;180(1):95-102. DOI: https://doi.org/10.1016/S0002-9378(99)70156-0</mixed-citation></ref><ref id="B53"><mixed-citation>Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992;71(1):169-180. DOI: https://doi.org/10.1016/0092-8674(92)90275-H</mixed-citation></ref><ref id="B54"><mixed-citation>Inoue I, Nakajima T, Williams CS, et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. Journal of Clinical Investigation. 1997;99(7):1786-1797. DOI: https://doi.org/10.1172/JCI119343</mixed-citation></ref><ref id="B55"><mixed-citation>Shahvaisizadeh F, Movafagh A, Omrani MD, et al. Synergistic effects of angiotensinogen&amp;minus; 217 G&amp;rarr; A and T704C (M235T) variants on the risk of severe preeclampsia. Journal of the Renin-Angiotensin-Aldosterone System. 2014;15(2):156-161. DOI: https://doi.org/10.1177/1470320312467555</mixed-citation></ref><ref id="B56"><mixed-citation>Balam-Ortiz E, Alfaro-Ruiz L, Carrillo K, et al. Variants and haplotypes in angiotensinogen gene are associated with plasmatic angiotensinogen level in Mexican population. American Journal of the Medical Sciences. 2011;342(3):205-211. DOI: https://doi.org/10.1097/MAJ.0b013e3182121020</mixed-citation></ref><ref id="B57"><mixed-citation>Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension. 2005;46(5):1077-1085. DOI: https://doi.org/10.1161/01.hyp.0000187899.34379.b0</mixed-citation></ref><ref id="B58"><mixed-citation>Yart L, Roset Bahmanyar E, Cohen M, et al. Role of the uteroplacental renin&amp;ndash;angiotensin system in placental development and function, and its implication in the preeclampsia pathogenesis. Biomedicines. 2021;9(10):1332. DOI: https://doi.org/10.3390/biomedicines9101332</mixed-citation></ref><ref id="B59"><mixed-citation>Lin R, Lei Y, Yuan Z, et al. Angiotensinogen gene M235T and T174M polymorphisms and susceptibility of pre‐eclampsia: a meta‐analysis. Annals of Human Genetics. 2012;76(5):377-386. DOI: https://doi.org/10.1111/j.1469-1809.2012.00722.x</mixed-citation></ref><ref id="B60"><mixed-citation>Choi H, Kang JY, Yoon HS, et al. Association of angiotensin-converting enzyme and angiotensinogen gene polymorphisms with preeclampsia. Journal of Korean Medical Science. 2004;19(2):253-257. DOI: https://doi.org/10.3346/jkms.2004.19.2.253</mixed-citation></ref><ref id="B61"><mixed-citation>Zitouni H, Ben Ali Gannoum M, et al. Contribution of angiotensinogen M235T and T174M gene variants and haplotypes to preeclampsia and its severity in (North African) Tunisians. Journal of the Renin-Angiotensin-Aldosterone System. 2018;19(1):1470320317753924. DOI: https://doi.org/10.1177/1470320317753924</mixed-citation></ref><ref id="B62"><mixed-citation>Akbar SA, Khawaja NP, Brown PR, et al. Angiotensin II type 1 and 2 receptors gene polymorphisms in preeclampsia and normal pregnancy in three different populations. Acta Obstetricia et Gynecologica Scandinavica. 2009;88(5):606-611. DOI: https://doi.org/10.1080/00016340902859307</mixed-citation></ref></ref-list></back></article>