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The effect of GPx-1 rs1050450 and MnSOD rs4880 polymorphisms on PE susceptibility: a case- control study

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Abstract

Preeclampsia (PE) is a serious pregnancy complication whose etiology is not fully understood. However, previous reports have suggested that oxidative stress and genetic variants may contribute to the development of PE. This study aimed to examine the relationship between the Glutathione peroxidase-1(GPx-1) and Manganese Superoxide dismutase (MnSOD) polymorphisms and preeclampsia (PE) risk in Iranian women. Genotyping of the studied women, including 179 preeclamptic cases and 202 controls, for GPx-1 rs1050450 and MnSOD rs4880 polymorphisms was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Our results showed a 1.7- to 1.6-fold increased risk of PE in the rs1050450 CT and CT + TT (dominant model) genotypes compared to CC genotype (OR = 1.7, 95%CI 1.1–2.7; P = 0.01 and OR = 1.6, 95%CI 1.1–2.4; P = 0.02; respectively). We also found a marked correlation between TC and CC genotypes of MnSOD rs4880 polymorphism and a 1.9- to 2.3-fold increase risk of PE (OR = 1.9, 95%CI 1.2–2.9; P = 0.005 and OR = 2.3, 95%CI 1–5.1; P = 0.04, respectively). The rs4880 MnSOD polymorphism was correlated with increased risk of PE in the allelic and dominant models (OR = 1.8, 95% CI 1.2–2.5, P = 0.002; OR = 1.9, 95%CI 1.3–3, P = 0.002, respectively). High frequency of TC/CC genotype of MnSOD rs4880 and CT genotypes of rs1050450 polymorphism in PE patients compared to controls showed the contribution of these variants to PE susceptibility.

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References

  1. Yoffe L, Gilam A, Yaron O, Polsky A, Farberov L, Syngelaki A, Nicolaides K, Hod M, Shomron N (2018) Early detection of preeclampsia using circulating small non-coding RNA. Sci Rep 8(1):3401

    PubMed  PubMed Central  Google Scholar 

  2. Harati-Sadegh M, Kohan L, Teimoori B, Salimi S (2018) The long non-coding RNA H19 rs217727 polymorphism is associated with PE susceptibility. J Cell Biochem 119(7):5473–5480

    CAS  PubMed  Google Scholar 

  3. Holland OJ, Cuffe JS, Nitert MD, Callaway L, Cheung KAK, Radenkovic F, Perkins AV (2018) Placental mitochondrial adaptations in preeclampsia associated with progression to term delivery. Cell Death Dis 9(12):1150

    PubMed  PubMed Central  Google Scholar 

  4. Michita RT, de Lima Kaminski V, Chies JAB (2018) Genetic variants in Preeclampsia: lessons from studies in Latin-American populations. Front Physiol 9:1771

    PubMed  PubMed Central  Google Scholar 

  5. Taravati A, Tohidi F (2018) Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwan J Obstet Gynecol 57(6):779–790

    PubMed  Google Scholar 

  6. Peng X, Lin Y, Li J, Liu M, Wang J, Li X, Liu J, Jia X, Jing Z, Huang Z (2016) Evaluation of glutathione peroxidase 4 role in preeclampsia. Sci Rep 6:33300

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Sánchez-Aranguren LC, Prada CE, Riaño-Medina CE, Lopez M (2014) Endothelial dysfunction and preeclampsia: role of oxidative stress. Front Physiol 5:372

    PubMed  PubMed Central  Google Scholar 

  8. Ighodaro O, Akinloye O (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med 54(4):287–293

    Google Scholar 

  9. Bakacak M, Kılınç M, Serin S, Ercan Ö, Köstü B, Avcı F, Kıran H, Kıran G (2015) Changes in copper, zinc, and malondialdehyde levels and superoxide dismutase activities in pre-eclamptic pregnancies. Med Sci Monit 21:2414

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Yahya MJ, Ismail PB, Nordin NB, Akim ABM, Yusuf BM, Shaariah W, Adam NLB, Zulkifli NF (2019) CNDP1, NOS3, and MnSOD polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients in Malaysia. J Nutr Metab 3:8736215

    Google Scholar 

  11. Salahshoor MR, Sohrabi M, Jalili F, Jalili P, Rezavand N, Haghnazari L, Jalili C (2019) No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD, and CAT genes on PCOS susceptibility. J Cell Biochem 120(2):2362–2369

    CAS  Google Scholar 

  12. Chiarello DI, Abad C, Rojas D, Toledo F, Vázquez CM, Mate A, Sobrevia L, Marín R (2018) Oxidative stress: normal pregnancy versus preeclampsia. Biochim et Biophys Acta. https://doi.org/10.1016/j.bbadis.2018.12.005

    Article  Google Scholar 

  13. Hansen AT, Jensen JMB, Hvas A-M, Christiansen M (2018) The genetic component of preeclampsia: A whole-exome sequencing study. PLoS ONE 13(5):e0197217

    PubMed  PubMed Central  Google Scholar 

  14. Da Costa LA, Badawi A, El-Sohemy A (2012) Nutrigenetics and modulation of oxidative stress. Ann Nutr Metab 60(Suppl. 3):27–36

    PubMed  Google Scholar 

  15. Yassaee F, Salimi S, Etemadi S, Yaghmaei M (2018) Comparison of CAT-21A/T gene polymorphism in women with Preeclampsia and Control Group. Adv Biomed Res 7:133

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim YJ, Park HS, Park MH, Suh SH, Pang M-G (2005) Oxidative stress-related gene polymorphism and the risk of preeclampsia. Eur J Obstet Gynecol Reprod Biol 119(1):42–46

    CAS  PubMed  Google Scholar 

  17. Liu D, Liu L, Hu Z, Song Z, Wang Y, Chen Z (2018) Evaluation of the oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population. Diabetes Vasc Dis Res 15(4):336–339

    CAS  Google Scholar 

  18. Turner JA (2010) Diagnosis and management of pre-eclampsia: an update. Int J Women’s Health 2:327

    CAS  Google Scholar 

  19. Degoul F, Sutton A, Mansouri A, Cepanec C, Valla D, Pessayre D, Fromenty B, Degott C, Beaugrand M (2001) Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease. Gastroenterology 120(6):1468–1474

    CAS  PubMed  Google Scholar 

  20. Xiong YM, Mo XY, Zou X, Song R, Sun W, Lu W, Chen Q, Yu Y, Zang W (2010) Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthr Cartil 18(6):817–824

    CAS  PubMed  Google Scholar 

  21. Rezaei M, Eskandari F, Mohammadpour-Gharehbagh A, Harati-Sadegh M, Teimoori B, Salimi S (2019) Hypomethylation of the miRNA-34a gene promoter is associated with Severe Preeclampsia. Clin Exp Hypertens 41(2):118–122

    CAS  Google Scholar 

  22. Mohammadpour-Gharehbagh A, Eskandari M, Sadegh MH, Nematollahi MH, Rezaei M, Rasouli A, Eskandari F, Heydarabad MZ, Teimoori B, Salimi S (2019) Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia. Apoptosis 24(3–4):301–311

    CAS  PubMed  Google Scholar 

  23. Tabatabai E, Salimi S, Mohammadoo-Khorasani M, Yaghmaei M, Mokhtari M, Farajian Mashhadi F, Naghavi A (2014) KE and EE genotypes of ICAM-1 gene K469E polymorphism is associated with severe preeclampsia. Dis Markers 2014:124941

    PubMed  PubMed Central  Google Scholar 

  24. Harati-Sadegh M, Kohan L, Teimoori B, Mehrabani M, Salimi S (2018) The association of the placental Hypoxia-inducible factor1-α polymorphisms and HIF1-α mRNA expression with preeclampsia. Placenta 67:31–37

    CAS  PubMed  Google Scholar 

  25. Salimi S, Saravani M, Yaghmaei M, Fazlali Z, Mokhtari M, Naghavi A, Farajian-Mashhadi F (2015) The early-onset preeclampsia is associated with MTHFR and FVL polymorphisms. Arch Gynecol Obstet 291(6):1303–1312

    CAS  PubMed  Google Scholar 

  26. Salimi S, Moudi B, Farajian Mashhadi F, Tavilani H, Hashemi M, Zand H, Yaghmaei M (2014) Association of functional polymorphisms in FAS and FAS Ligand genes promoter with pre-eclampsia. J Obstet Gynaecol Res 40(5):1167–1173

    CAS  PubMed  Google Scholar 

  27. Aouache R, Biquard L, Vaiman D, Miralles F (2018) Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci 19(5):1496

    PubMed Central  Google Scholar 

  28. Williams PJ, Pipkin FB (2011) The genetics of pre-eclampsia and other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 25(4):405–417

    PubMed  PubMed Central  Google Scholar 

  29. Mannaerts D, Faes E, Cos P, Briede JJ, Gyselaers W, Cornette J, Gorbanev Y, Bogaerts A, Spaanderman M, Van Craenenbroeck E (2018) Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function. PLoS ONE 13(9):e0202919

    PubMed  PubMed Central  Google Scholar 

  30. Siddiqui IA, Jaleel A, Tamimi W, Al Kadri HM (2010) Role of oxidative stress in the pathogenesis of preeclampsia. Arch Gynecol Obstet 282(5):469–474

    CAS  PubMed  Google Scholar 

  31. Leal CA, Schetinger MR, Leal DB, Morsch VM, da Silva AS, Rezer JF, de Bairros AV, Jaques JAdS (2011) Oxidative stress and antioxidant defenses in pregnant women. Redox Rep 16(6):230–236

    CAS  PubMed  Google Scholar 

  32. Lubos E, Loscalzo J, Handy DE (2011) Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 15(7):1957–1997

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Roland-Zejly L, Moisan V, St-Pierre I, Bilodeau J-F (2011) Altered placental glutathione peroxidase mRNA expression in preeclampsia according to the presence or absence of labor. Placenta 32(2):161–167

    CAS  PubMed  Google Scholar 

  34. Zmorzyński S, Świderska-Kołacz G, Koczkodaj D, Filip AA (2015) Significance of polymorphisms and expression of enzyme-encoding genes related to glutathione in hematopoietic cancers and solid tumors. BioMed Res Int 2015:853573

    PubMed  PubMed Central  Google Scholar 

  35. Cao M, Mu X, Jiang C, Yang G, Chen H, Xue W (2014) Single-nucleotide polymorphisms of GPX1 and MnSOD and susceptibility to bladder cancer: a systematic review and meta-analysis. Tumor Biol 35(1):759–764

    CAS  Google Scholar 

  36. Habyarimana T, Bakri Y, Mugenzi P, Mazarati JB, Attaleb M, El Mzibri M (2018) Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda. Mol Genet Genomic Med 6(2):268–275

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Jablonska E, Gromadzinska J, Peplonska B, Fendler W, Reszka E, Krol MB, Wieczorek E, Bukowska A, Gresner P, Galicki M (2015) Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1. BMC Cancer 15(1):657

    PubMed  PubMed Central  Google Scholar 

  38. Tang T, Prior S, Li K, Ireland H, Bain S, Hurel S, Cooper J, Humphries S, Stephens J (2012) Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis 22(5):417–425

    CAS  PubMed  Google Scholar 

  39. Gao H, Liu C, Lin P, Xu L, Li X, Chen Y, Cheng B, Li A, Liu S (2016) Effects of GSTP1 and GPX1 polymorphisms on the risk of preeclampsia in chinese han women. Cell Physiol Biochem 39(5):2025–2032

    CAS  PubMed  Google Scholar 

  40. Candas D, Li JJ (2014) MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxid Redox Signal 20(10):1599–1617

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Abbasi M, Daneshpour MS, Hedayati M, Mottaghi A, Pourvali K, Azizi F (2018) The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study. Nutr Metab 15(1):25

    Google Scholar 

  42. Zhang J, Masciocchi M, Lewis D, Sun W, Liu A, Wang Y (2008) Placental anti-oxidant gene polymorphisms, enzyme activity, and oxidative stress in preeclampsia. Placenta 29(5):439–443

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Jabir FA, Hoidy WH (2018) Pharmacogenetics as personalized medicine: association investigation of SOD2 rs4880, CYP2C19 rs4244285, and FCGR2A rs1801274 polymorphisms in a breast cancer population in Iraqi women. Clin Breast Cancer 18(5):e863–e868

    CAS  PubMed  Google Scholar 

  44. Xu M, Xu M, Han L, Yuan C, Mei Y, Zhang H, Chen S, Sun K, Zhu B (2017) Role for functional SOD2 polymorphism in pulmonary arterial hypertension in a chinese population. Int J Environ Res Public Health 14(3):266

    PubMed Central  Google Scholar 

  45. Botre C, Shahu A, Adkar N, Shouche Y, Ghaskadbi S, Ashma R (2015) Superoxide dismutase 2 polymorphisms and osteoporosis in Asian Indians: a genetic association analysis. Cell Mol Biol Lett 20(4):685–697

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work is extracted from the Residency’s dissertation (Number 8214) at Zahedan University of Medical Sciences. We would like to thank all of the participants who made it possible to conduct the study.

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Correspondence to Saeedeh Salimi.

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The current study was approved by the ethics committee of Zahedan University of Medical Sciences.

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Teimoori, B., Moradi-shahrebabak, M., Razavi, M. et al. The effect of GPx-1 rs1050450 and MnSOD rs4880 polymorphisms on PE susceptibility: a case- control study. Mol Biol Rep 46, 6099–6104 (2019). https://doi.org/10.1007/s11033-019-05045-6

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