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Hypertension Research
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Methylenetetrahydrofolate Reductase C677T and Glutathione S−Transferase P1 A313G Are Associated with a Reduced Risk of Preeclampsia in Maya-Mestizo Women
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  • Original Article
  • Published: 01 May 2008

Methylenetetrahydrofolate Reductase C677T and Glutathione S−Transferase P1 A313G Are Associated with a Reduced Risk of Preeclampsia in Maya-Mestizo Women

  • Patricia Canto1,
  • Thelma Canto-Cetina2,
  • Rocio Juárez-Velázquez3,
  • Haydee Rosas-Vargas3,
  • Héctor Rangel-Villalobos4,
  • Samuel Canizales-Quinteros5,
  • Ana C Velázquez-Wong3,
  • María T Villarreal-Molina5,
  • Genny Fernández6 &
  • …
  • Ramón Coral-Vázquez3 

Hypertension Research volume 31, pages 1015–1019 (2008) Cite this article

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Abstract

Preeclampsia, a common complication of pregnancy, is characterized by elevated blood pressure and proteinuria developing after 20 weeks’ gestational age. Susceptibility to this syndrome is believed to have a genetic component. The aim of this study was to investigate whether or not the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and glutathione S−transferase P1 (GSTP1) A313G polymorphisms are associated with preeclampsia in Maya-Mestizo women. A case-control study was performed, in which 125 preeclamptic patients and 274 healthy controls were genotyped for the MTHFR C677T and GSTP1 A313G polymorphisms by real-time PCR allelic discrimination. Allele and genotype frequencies were compared using the χ2 tests. The MTHFR 677T allele and the 677TT genotype were significantly more frequent in the controls, suggesting an association with a decreased risk of preeclampsia (p=0.017 and p=0.007, respectively). Similarly, GSTP1 313GG/GC genotypes and the G allele were more frequent in controls, showing a significant association with reduced risk of preeclampsia (p=0.008 and p=0.013, respectively). Our results suggest, for the first time, that the MTHFR 677T and GSTP1 313G polymorphisms confer a significantly decreased risk of developing preeclampsia in the Mexican Maya-Mestizo population.

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References

  1. Roberts JM, Cooper DW : Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357: 53–56.

    Article  CAS  Google Scholar 

  2. López-Jaramillo P, Casas JP, Serrano N : Preeclampsia: from epidemiological observations to molecular mechanisms. Braz J Med Biol Res 2001; 34: 1227–1235.

    Article  Google Scholar 

  3. Lain KY, Roberts JM : Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA 2002; 287: 3183–3186.

    Article  Google Scholar 

  4. Kilpatrick DC, Liston WA, Gibson F, Livingstone J : Association between susceptibility to pre-eclampsia within families and HLA DR4. Lancet 1989; 2: 1063–1065.

    Article  CAS  Google Scholar 

  5. O'Brien M, Dausset J, Carosella ED, Moreau P : Analysis of the role of HLA-G in preeclampsia. Hum Immunol 2000; 61: 1126–1131.

    Article  CAS  Google Scholar 

  6. Vollset SE, Refsum H, Irgens LM, et al: Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr 2000; 71: 962–968.

    Article  CAS  Google Scholar 

  7. Powers RW, Evans RW, Majors AK, et al: Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998; 179: 1605–1611.

    Article  CAS  Google Scholar 

  8. Lopez-Quesada E, Vilaseca MA, Lailla JM : Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia. Eur J Obstet Gynecol Reprod Biol 2003; 108: 45–49.

    Article  CAS  Google Scholar 

  9. Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T : Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J Med Genet 1997; 34: 525–526.

    Article  CAS  Google Scholar 

  10. Frosst P, Blom HJ, Milos R, et al: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111–113.

    Article  CAS  Google Scholar 

  11. Dekker GA, Sibai BM : Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998; 179: 1359–1375.

    Article  CAS  Google Scholar 

  12. Zusterzeel PL, Peters WH, De Bruyn MA, Knapen MF, Merkus HM, Steegers EA : Glutathione S−transferase isoenzymes in decidua and placenta of preeclamptic pregnancies. Obstet Gynecol 1999; 94: 1033–1038.

    CAS  PubMed  Google Scholar 

  13. Zusterzeel PL, Visser W, Peters WH, Merkus HW, Nelen WL, Steegers EA : Polymorphism in the glutathione S−transferase P1 gene and risk for preeclampsia. Obstet Gynecol 2000; 96: 50–54.

    CAS  PubMed  Google Scholar 

  14. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000; 183: S1–S22.

  15. Kempter B, Grossbadern K : Quick preparation of high molecular weight DNA by freezing. Trends Genet 1992; 8: 226.

    Article  Google Scholar 

  16. Duran N, Couoh J : Epidemilogía de la preeclampsia-eclampsia de una muestra en Yucatán. Ginecol Obstet Mex 1999; 67: 571–577 ( in Spanish).

    Google Scholar 

  17. Pértegas Díaz S, Pita Fernández S : Unidad de Epidemiología Clínica y Bioestadística. Complexo Hospitalario-Universitario Juan Canalejo. A Coruña (España). Cad Aten Primaria 2003; 10: 59–63 ( in Spanish).

    Google Scholar 

  18. Ness RB, Roberts JM : Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet Gynecol 1996; 175: 1365–1370.

    Article  CAS  Google Scholar 

  19. De Maat MP, Jansen MW, Hille ET, et al: Preeclampsia and its interaction with common variants in thrombophilia genes. J Thromb Haemost 2004; 2: 1588–1593.

    Article  CAS  Google Scholar 

  20. Also-Rallo E, Lopez-Quesada E, Urreizti R, et al: Polymorphisms of genes involved in homocysteine metabolism in preeclampsia and in uncomplicated pregnancies. Eur J Obstet Gynecol Reprod Biol 2005; 120: 45–52.

    Article  CAS  Google Scholar 

  21. Kosmas IP, Tatsioni A, Ioannidis JP : Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J Hypertens 2004; 22: 1655–1662.

    Article  CAS  Google Scholar 

  22. Mello G, Parretti E, Marozio L, et al: Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. Hypertension 2005; 46: 1270–1274.

    Article  CAS  Google Scholar 

  23. Le Marchand L, Wilkens LR, Kolonel LN, Henderson BE : The MTHFR C677T polymorphism and colorectal cancer: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 2005; 14: 1198–1203.

    Article  CAS  Google Scholar 

  24. Hubner RA, Houlston RS : MTHFR C677T and colorectal cancer risk: a meta-analysis of 25 populations. Int J Cancer 2006; 120: 1027–1035.

    Article  Google Scholar 

  25. Zintzaras E, Koufakis T, Ziakas PD, Rodopoulou P, Giannouli S, Voulgarelis M : A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia. Eur J Epidemiol 2006; 21: 501–510.

    Article  CAS  Google Scholar 

  26. Pérez-Mutul J, Gonzalez-Herrera L, Sosa-Cabrera T, Martinez-Olivares R : A mutation in the 5,10-methylenetetrahydrofolate reductase gene is not associated with preeclampsia in women of southeast México. Arch Med Res 2004; 35: 231–234.

    Article  Google Scholar 

  27. Dávalos IP, Moran MC, Martinez-Abundis E, et al: Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia. Blood Cell Mol Dis 2005; 35: 66–69.

    Article  Google Scholar 

  28. Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J : Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S−transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 1997; 272: 10004–10012.

    Article  CAS  Google Scholar 

  29. Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA : Human glutathione S−transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 1998; 19: 275–280.

    Article  CAS  Google Scholar 

  30. Ohta K, Kobashi G, Hata A, et al: Association between a variant of the glutathione S−transferase P1 gene (GSTP1) and hypertension in pregnancy in Japanese: interaction with parity, age, and genetic factors. Semin Thromb Hemost 2003; 29: 653–659.

    Article  CAS  Google Scholar 

  31. Gebhardt GS, Peters WH, Hillermann R, et al: Maternal and fetal single nucleotide polymorphisms in the epoxide hydrolase and gluthatione S−transferase P1 genes are not associated with pre-eclampsia in the Coloured population of the Western Cape, South Africa. J Obstet Gynaecol 2004; 24: 866–872.

    Article  CAS  Google Scholar 

  32. Lee YL, Lin YC, Lee YC, Wang JY, Hsiue TR, Guo YL : Glutathione S−transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma. Clin Exp Allergy 2004; 34: 1707–1713.

    Article  CAS  Google Scholar 

  33. Stanulla M, Schrappe M, Brechlin AM, Zimmermann M, Welte K : Polymorphisms within glutathione S−transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study. Blood 2000; 95: 1222–1228.

    CAS  PubMed  Google Scholar 

  34. Dasgupta RK, Adamson PJ, Davies FE, et al: Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma. Blood 2003; 102: 2345–2350.

    Article  CAS  Google Scholar 

  35. Hohaus S, Di Ruscio A, Di Febo A, et al: Glutathione S−transferase P1 genotype and prognosis in Hodgkin's lymphoma. Clin Cancer Res 2005; 11: 2175–2179.

    Article  CAS  Google Scholar 

  36. Ertunc D, Aban M, Tok EC, Tamer L, Arslan M, Dilek S : Glutathione- S−transferase P1 gene polymorphism and susceptibility to endometriosis. Hum Reprod 2005; 20: 2157–2161.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Unit in Developmental Biology, National Medical Center XXI Century, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico

    Patricia Canto

  2. Reproductive Health and Genetics Department, Reproduction Biology Laboratory, “Dr. Hideyo Noguchi” Research Center, Merida, Mexico

    Thelma Canto-Cetina

  3. Medical Research Unit in Human Genetics, National Medical Center XXI Century, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico

    Rocio Juárez-Velázquez, Haydee Rosas-Vargas, Ana C Velázquez-Wong & Ramón Coral-Vázquez

  4. Life and Medical Science Department, Molecular Genetics Laboratory (CU Cienega-U de G), Centro Universitario de la Cienega, University of Guadalajara, Ocotlan, Mexico

    Héctor Rangel-Villalobos

  5. Molecular Biology and Genomic Medicine Unit, Instituto Nacional de Ciencias Medicas y Nutricion “Salvador Zubiran”, Mexico, D.F., Mexico

    Samuel Canizales-Quinteros & María T Villarreal-Molina

  6. Perinatology Service of the Hospital Materno Infantil, S.S. Merida, Mexico

    Genny Fernández

Authors
  1. Patricia Canto
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Correspondence to Ramón Coral-Vázquez.

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Canto, P., Canto-Cetina, T., Juárez-Velázquez, R. et al. Methylenetetrahydrofolate Reductase C677T and Glutathione S−Transferase P1 A313G Are Associated with a Reduced Risk of Preeclampsia in Maya-Mestizo Women. Hypertens Res 31, 1015–1019 (2008). https://doi.org/10.1291/hypres.31.1015

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  • Received: 07 September 2007

  • Accepted: 19 December 2007

  • Issue date: 01 May 2008

  • DOI: https://doi.org/10.1291/hypres.31.1015

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Keywords

  • glutathione S–transferase P1 (GSTP1) A313G
  • 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T
  • Maya-Mestizo women
  • preeclampsia

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