Methylenetetrahydrofolate Reductase Enzyme Level and Antioxidant Activity in Women with Gestational Hypertension and Pre-eclampsia in Lagos, Nigeria

  • V. O. OsunkaluEmail author
  • I. A. Taiwo
  • C. C. Makwe
  • O. J. Akinsola
  • R. A. Quao
Original Article



Deficiencies of enzymes in the folate cycle may lead to the generation of homocysteine, a toxic metabolic intermediate with pro-oxidant effect and ability to induce oxidant stress and lipid peroxidation as part of the pathophysiological process in gestational hypertension (GH) and pre-eclampsia (PE).


The aim of this study is to assess the reliability of plasma homocysteine (hcy) 5, 10 methylenetetrahydrofolate reductase (MTHFR) enzyme and oxidative stress parameters as indicators of aetio-pathogenesis and severity of gestational hypertension and pre-eclampsia.

Subjects and Methods

This was a comparative cross-sectional study conducted over 6 months. Two hundred pregnant women were recruited from two sites. They were divided into gestation hypertension (n = 40), pre-eclampsia (n = 60) and control groups (n = 100). Parameters evaluated for statistical analysis were MTHFR enzyme level, plasma homocysteine and malondialdehyde (MDA) levels, with glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities.


Mean plasma hcy level and MDA were significantly higher in pre-eclampsia and gestational hypertension when compared to control group (p < 0.05). However, MTHFR enzyme level, GSH, SOD and CAT were significantly higher in normotensive females when compared to PE and GH subgroups (p < 0.05). Pre-eclampsia was significantly associated with an increased risk of lipid peroxidation (OR = 4.923; p = 0.007).


Pre-eclampsia and gestational hypertension are associated with marked homocysteine metabolic derangement and increased lipid peroxidation induced by oxidative stress and reduced MTHFR enzyme activity which may be the significant risk factors in the aetio-pathogenesis of GH and PE.


Pre-eclampsia Gestational hypertension Antioxidant Lipid peroxidation 


Compliance with Ethical Standards

Conflict of interest

Vincent Osunkalu, Idowu Taiwo, Christian Makwe, Oluwatosin Akinsola and Rachel Quao have declared that they have no conflict of interest. All processes involved in this research project were self-sponsored.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Health Research and Ethics Committee of the Lagos University Teaching Hospital and Lagos State Hospital Management Board) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Informed Consent

Informed consent was obtained from all patients for being included in the study.


  1. 1.
    Garovic VD, August P. Preeclampsia and the future risk of hypertension: the pregnant evidence. Curr Hypertens Rep. 2013;15(2):114–21.CrossRefGoogle Scholar
  2. 2.
    Berhan Y, Gezahegn E. Maternal mortality predictors in women with hypertensive disorders of pregnancy: a retrospective cohort study. Ethiop J Health Sci. 2015;25(1):89–98.CrossRefGoogle Scholar
  3. 3.
    Singh S, Bissallah E, Shehu A, et al. Hypertensive disorders in pregnancy among pregnant women in a Nigerian Teaching Hospital. Niger Med J. 2014;55(5):384–8.CrossRefGoogle Scholar
  4. 4.
    Schaap T, Knight M, Zwart JJ, et al. Eclampsia, a comparison within the International Network of Obstetric Surveillance Systems (INOSS). BJOG. 2014;121:1521–8.CrossRefGoogle Scholar
  5. 5.
    Dreyfus M, Weber P, Zieleskiewicz L. Maternal deaths due to hypertensive disorders. Results from the French confidential enquiry into maternal deaths, 2010–2012. Gynecol Obstet Fertil Senol. 2017;45(12S):S38–42.Google Scholar
  6. 6.
    Goldenberg RL, McClure EM, Macguire ER, et al. Lessons for low-income regions following the reduction in hypertension-related maternal mortality in high-income countries. Int J Gynaecol Obstet. 2011;113(2):91–5.CrossRefGoogle Scholar
  7. 7.
    Oye-Adeniran B, Odeyemi K, Gbadegesin A, et al. Causes of maternal mortality in Lagos State. Nigeria. Ann Trop Med Public Health. 2014;7:177–81.CrossRefGoogle Scholar
  8. 8.
    Steegers EA, von Dadelszen P, Duvekot JJ, et al. Pre-eclampsia. Lancet. 2010;376(9741):631–44.CrossRefGoogle Scholar
  9. 9.
    Nishizawa H, Ota S, Suzuki M, et al. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. Reprod Biol Endocrinol. 2011;9:107.CrossRefGoogle Scholar
  10. 10.
    Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014;4(2):97–104.CrossRefGoogle Scholar
  11. 11.
    Pennington KA, Schlitt JM, Jackson DL, et al. Preeclampsia: multiple approaches for a multifactorial disease. Dis Model Mech. 2012;5(1):9–18.CrossRefGoogle Scholar
  12. 12.
    Wu F, Tian FJ, Lin Y, et al. Oxidative stress: placenta function and dysfunction. Am J Reprod Immunol. 2016;76(4):258–71.CrossRefGoogle Scholar
  13. 13.
    Cohen JM, Kramer MS, Platt RW, et al. The association between maternal antioxidant levels in midpregnancy and preeclampsia. Am J Obstet Gynecol. 2015;213(5):695 e1–13.CrossRefGoogle Scholar
  14. 14.
    Silva DM, Marreiro Ddo N, Moita Neto JM, et al. Oxidative stress and immunological alteration in women with preeclampsia. Hypertens Pregnancy. 2013;32(3):304–11.CrossRefGoogle Scholar
  15. 15.
    Szarka A, Rigo J Jr, Lazar L, et al. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol. 2010;11:59.CrossRefGoogle Scholar
  16. 16.
    Wang XM, Wu HY, Qiu XJ. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and risk of preeclampsia: an updated meta-analysis based on 51 studies. Arch Med Res. 2013;44(3):159–68.CrossRefGoogle Scholar
  17. 17.
    Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol. 2010;63(6):534–43.CrossRefGoogle Scholar
  18. 18.
    Aouache R, Biquard L, Vaiman D, et al. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci. 2018;19(5):1496. Scholar
  19. 19.
    Karacay O, Sepici-Dincel A, Karcaaltincaba D, et al. A quantitative evaluation of total antioxidant status and oxidative stress markers in preeclampsia and gestational diabetic patients in 24–36 weeks of gestation. Diabetes Res Clin Pract. 2010;89(3):231–8.CrossRefGoogle Scholar
  20. 20.
    Jastroch M, Divakaruni AS, Mookerjee S, et al. Mitochondrial proton and electron leaks. Essays Biochem. 2010;47:53–67.CrossRefGoogle Scholar
  21. 21.
    Sultana Z, Maiti K, Aitken J, et al. Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes. Am J Reprod Immunol. 2017;77(5):e12653.CrossRefGoogle Scholar
  22. 22.
    Sun F, Qian W, Zhang C, et al. Correlation of maternal serum homocysteine in the first trimester with the development of gestational hypertension and preeclampsia. Med Sci Monit. 2017;23:5396–401.CrossRefGoogle Scholar
  23. 23.
    Wadhwani NS, Patil VV, Mehendale SS, et al. Increased homocysteine levels exist in women with preeclampsia from early pregnancy. J Matern Fetal Neonatal Med. 2016;29(16):2719–25.Google Scholar
  24. 24.
    Maru L, Verma M, Jinsiwale N. Homocysteine as predictive marker for pregnancy-induced hypertension—a comparative study of homocysteine levels in normal versus patients of PIH and its complications. J Obstet Gynaecol India. 2016;66(Suppl 1):167–71.CrossRefGoogle Scholar
  25. 25.
    Acilmis YG, Dikensoy E, Kutlar AI, et al. Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia. J Obstet Gynaecol Res. 2011;37(1):45–50.CrossRefGoogle Scholar
  26. 26.
    Kumar Avinash, Palfrey HA, Pathak R, et al. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond). 2017;14:78.CrossRefGoogle Scholar
  27. 27.
    Navneet OS. Antioxidant assay in vivo and vitro. Int J Phytopharm. 2014;5(1):51–8.Google Scholar
  28. 28.
    Fatai IM, Imaga NOA, Gbenle GO. Biochemical investigations into the effects of coadministration of ciprofloxacin and nicosan. Afr J Pharm Pharmacol. 2013;7(39):2674–9.CrossRefGoogle Scholar
  29. 29.
    Cekić S, Zlatanović G, Cvetković T, et al. Oxidative stress in cataractogenesis. Bosn J Basic Med Sci. 2010;10(3):265–9.CrossRefGoogle Scholar
  30. 30.
    Malek M, Riadh BM, Fatma M, et al. Lipid peroxidation, proteins modifications, anti-oxidant enzymes activities and selenium deficiency in the plasma of hashitoxicosis patients. Ther Adv Endocrinol Metab. 2015;6(5):181–8.CrossRefGoogle Scholar
  31. 31.
    Škovierová H, Vidomanová E, Mahmood S, et al. The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci. 2016;17(10):1733. Scholar
  32. 32.
    Lee R, Margaritis M, Channon KM, et al. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem. 2012;19(16):2504–20.CrossRefGoogle Scholar
  33. 33.
    Gohil JT, Patel PK, Gupta P. Evaluation of oxidative stress and antioxidant defence in subjects of preeclampsia. J Obstet Gynaecol india. 2011;61(6):638–40.CrossRefGoogle Scholar
  34. 34.
    Adeniji AO, Oparinde DP. Comparison of lipid peroxidation and anti-oxidant activities in pre-eclamptic & normal pregnancies in nigerian population. Int J Clin Med. 2013;4:239–43.CrossRefGoogle Scholar
  35. 35.
    Liu HH, Shih TS, Huang HR, et al. Plasma homocysteine is associated with increased oxidative stress and antioxidant enzyme activity in welders. Sci World J. 2013. Scholar
  36. 36.
    Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016;15(1):71. Scholar
  37. 37.
    Poston L, Igosheva N, Mistry HD, et al. Role of oxidative stress and antioxidant supplementation in pregnancy disorders. Am J Clin Nutr. 2011;94(suppl):1980S–5S.CrossRefGoogle Scholar

Copyright information

© Federation of Obstetric & Gynecological Societies of India 2019

Authors and Affiliations

  1. 1.Department of Haematology and Blood Transfusion, College of MedicineUniversity of LagosLagosNigeria
  2. 2.Department of Cell Biology and GeneticsUniversity of LagosLagosNigeria
  3. 3.Department of Obstetrics and Gynaecology, College of MedicineUniversity of LagosLagosNigeria
  4. 4.Department of Community Health and Primary CareLagos University Teaching HospitalLagosNigeria

Personalised recommendations