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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Roberts JM, Cooper DW : Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357: 53–56.
López-Jaramillo P, Casas JP, Serrano N : Preeclampsia: from epidemiological observations to molecular mechanisms. Braz J Med Biol Res 2001; 34: 1227–1235.
Lain KY, Roberts JM : Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA 2002; 287: 3183–3186.
Kilpatrick DC, Liston WA, Gibson F, Livingstone J : Association between susceptibility to pre-eclampsia within families and HLA DR4. Lancet 1989; 2: 1063–1065.
O'Brien M, Dausset J, Carosella ED, Moreau P : Analysis of the role of HLA-G in preeclampsia. Hum Immunol 2000; 61: 1126–1131.
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.
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.
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.
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.
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.
Dekker GA, Sibai BM : Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998; 179: 1359–1375.
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.
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.
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.
Kempter B, Grossbadern K : Quick preparation of high molecular weight DNA by freezing. Trends Genet 1992; 8: 226.
Duran N, Couoh J : Epidemilogía de la preeclampsia-eclampsia de una muestra en Yucatán. Ginecol Obstet Mex 1999; 67: 571–577 ( in Spanish).
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).
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.
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.
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.
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.
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.
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.
Hubner RA, Houlston RS : MTHFR C677T and colorectal cancer risk: a meta-analysis of 25 populations. Int J Cancer 2006; 120: 1027–1035.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dasgupta RK, Adamson PJ, Davies FE, et al: Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma. Blood 2003; 102: 2345–2350.
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.
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.
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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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DOI: https://doi.org/10.1291/hypres.31.1015
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