skip to main content

Low sEng Level in Preeclampsia with MFTHFR Gene Polymorphism Suggesting a Protective Factor

1Faculty of Medicine, Universitas Diponegoro, Indonesia

2Faculty of Medicine, Universitas Yarsi, Indonesia

3Faculty of Public Health, Universitas Diponegoro, Indonesia

Received: 11 Sep 2025; Revised: 24 Nov 2025; Accepted: 28 Nov 2025; Available online: 24 Dec 2025; Published: 31 Dec 2025.
Open Access Copyright (c) 2025 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:
Abstract

Background: Preeclampsia is one of the most serious complications of pregnancy and the leading cause of maternal and fetal mortality. Various studies have shown that Glutathione Peroxidase (GPx) deficiency and increased Soluble endoglin (sEng) level are consistently associated with the incidence of preeclampsia. Several studies also show the role of MTHFR A1298C and C677T gene polymorphisms in preeclampsia.

Objective: This study investigated association between blood GPx, sEng levels, MTHFR A1298C and C677T gene polymorphisms in Preeclampsia.

Methods: This analytic observational case-control study was conducted on 70 cases of preeclampsia and 70 controls. Blood GPx and sEng levels were measured using Enzyme Linked Immunosorbent Assay (ELISA). MTHFR A1298C and C677T gene polymorphism was genotyped using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The data obtained were analyzed using the Mann-Whitney U test, chi-square test, and independent T-test.

Results: There were no significant differences in GPx levels or MTHFR A1298C/C677T genotype distribution between groups. sEng levels were significantly higher in the preeclampsia group than controls (p=0.001). ROC analysis identified a cut-off of 7.75 ng/mL. Among preeclampsia patients, those with the MTHFR 1298AC/CC genotypes had lower sEng levels than wildtype (p=0.027), suggesting a potential protective effect. No association was found for C677T.

Conclusion: We found no significant difference in GPx level, MTHFR A1298C and C677T gene polymorphism between preeclampsia and control group. Soluble endoglin (sEng) level in the preeclampsia group (mean: 11.0±5.22) were significantly different (p=0.001) compared to the control group (mean: 8.1±5.31). Increased level of sEng is associated with incidence of preeclampsia. A key finding in this study is the significantly lower sEng levels observed in preeclampsia patients carrying the MTHFR 1298AC and 1298CC alleles compared to the control group (p=0.027). This indicates a protective factor where in preeclampsia with MTHFR gene alleles 1298AC and 1298CC sEng levels are lower compared to wildtype.

Note: This article has supplementary file(s).

Fulltext View|Download |  Research Results
Research Data
Subject
Type Research Results
  Download (39KB)    Indexing metadata
 Cover Letter
Covering Letter
Subject
Type Cover Letter
  Download (16KB)    Indexing metadata
 Copyright Transfer Agreement
Copyright Transfer Agreement
Subject
Type Copyright Transfer Agreement
  Download (290KB)    Indexing metadata
Keywords: Glutathione; Peroxidase; MFTHR gene polymorphism; Preeclampsia; Soluble endoglin

Article Metrics:

  1. American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222. Obstet Gynecol. 2020;135(6):e237–60. doi: 10.1097/AOG.0000000000003891
  2. McElwain CJ, Tuboly E, McCarthy FP, McCarthy CM. Mechanisms of endothelial dysfunction in pre-eclampsia and gestational diabetes mellitus: windows into future cardiometabolic health? Front Endocrinol (Lausanne). 2020;11:655. doi: 10.3389/fendo.2020.00655
  3. Guerby P, Tasta O, Swiader A, Pont F, Bujold E, Parant O, et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. Redox Biol. 2021;40:101861. doi: 10.1016/j.redox.2021.101861
  4. Margioula-Siarkou G, Margioula-Siarkou C, Petousis S, Margaritis K, Alexandratou M, Dinas K, et al. Soluble endoglin concentration in maternal blood as a diagnostic biomarker of preeclampsia: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2021;258:366–81. doi: 10.1016/j.ejogrb.2021.01.039
  5. Mustiqa Febriniata, Dian Ariningrum, & Sienny Linawaty. (2025). Serum Soluble Endoglin (sEng) as A Predictor of Preeclampsia Severity. INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY, 32(1), 81–85. https://doi.org/10.24293/ijcpml.v32i1.2403
  6. Hu Y, Wang A, Yi K. MTHFR A1298C polymorphism and risk of preeclampsia: A meta-analysis. Clin Exp Obstet Gynecol. 2023;50(12):266. doi: 10.31083/j.ceog5012266
  7. Varzari A, Deyneko IV, Tudor E, Turcan S. Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation. Meta Gene. 2016;7:76–82. doi: 10.1016/j.mgene.2015.12.002
  8. Bisht S, Chawla B, Dada R. Oxidative Stress and Polymorphism in MTHFR SNPs (677 and 1298) in Paternal Sperm DNA is Associated with an Increased Risk of Retinoblastoma in Their Children: A Case-Control Study. J Pediatr Genet. 2018;7(3):103-113. doi: 10.1055/s-0038-1667037
  9. Rao J, Chen Y, Chen X, Wu R, Luo S, Lin Q, et al. The gene polymorphisms of eNOS and MTHFR modulates the development of preeclampsia in Han population. Heliyon. 2023;9(12):e22223. doi: 10.1016/j.heliyon.2023.e22223
  10. Rahimi Z, Malek-Khosravi S, Rahimi Z, Jalilvand F, Parsian A. MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress. Clin Biochem. 2013;46(1-2):143-147. doi: 10.1016/j.clinbiochem.2012.10.020
  11. Castiglia P, Sanna V, Azara A, De Miglio MR, Murgia L, Pira G, et al. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: A Sardinian preliminary case-control study. Int J Med Sci. 2019;16(8):1089–95. doi: 10.7150/ijms.32162
  12. Ahmad IM, Zimmerman MC, Moore TA. Oxidative stress in early pregnancy and the risk of preeclampsia. Pregnancy Hypertens. 2019;18:99–102. doi: 10.1016/j.preghy.2019.09.014
  13. Afrose D, Chen H, Ranashinghe A, Liu C chi, Henessy A, Hansbro PM, et al. The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis. Biol Sex Differ. 2022 Dec 1;13(1). doi: 10.1186/s13293-022-00436-0
  14. Leaños-Miranda A, Navarro-Romero CS, Sillas-Pardo LJ, Ramírez Valenzuela KL, Isordia-Salas I, Jiménez-Trejo LM. Soluble endoglin as a marker for preeclampsia, its severity, and the occurrence of adverse outcomes. Hypertension.2019;74(4):991-doi: 10.1161/HYPERTENSIONAHA.119.13348
  15. Mahmood S, Younus A, Nathaniel S, Younas H. MTHFR A1298C polymorphism: A predictor of reduced risk of preeclampsia in Punjab, Pakistan. Hypertens Pregnancy. 2023;42(1):2187621. doi: 10.1080/10641955.2023.2187621
  16. Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642-649. doi: 10.1038/nm1429
  17. Gregory AL, Xu G, Sotov V, Letarte M. Review: The enigmatic role of endoglin in the placenta. Placenta. 2014;28:593–9. doi: 10.1016/j.placenta.2013.10.020
  18. Gu Y, Lewis DF, Wang Y. Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab. 2008;93(1):260-266. doi: 10.1210/jc.2007-1550
  19. Sachan R, Patel ML, Dhiman S, Gupta P, Sachan P, Shyam R. Diagnostic and prognostic significance of serum soluble endoglin levels in preeclampsia and eclampsia. Adv Biomed Res. 2016;5(1):119. doi: 10.4103/2277-9175.186993
  20. Khidri FF, Waryah Y M, Ali FK, Shaikh H, Ujjan ID, Waryah AM. MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case-control study. BMC Med Genet. 2019;20(1):163. doi: 10.1186/s12881-019-0905-9

Last update:

No citation recorded.

Last update:

No citation recorded.