Rojas JC, Luna M, Rangel-Nava H, Baños D, Collados MT

Language: Spanish
References: 12
Page: 401-409
PDF size: 313.21 Kb.

ABSTRACT

Background: The presence of thrombosis in preeclampsia suggests that endothelial function could play an important role in its pathogenesis.
Objective: Determine the association between markers of genetic thrombophilia, endothelial activation and preeclampsia.
Material and method: Prospective study of cases and controls to determine the factor V Leiden existence, protrombin G20210A, methylenetetrahydrofolate reductase C677T, activated protein C resistance and levels of von Willebrand factor and the sFlt1 receptor were determined in 28 women with preeclampsia and 41 pregnant controls.
Results: Methylenetetrahydrofolate reductase C677T had a high allelic frequency (0.50). Even in the absence of factor V Leiden, there were significant differences in the prevalence of activated protein C resistance and abnormal levels of sFlt1 between patients with preeclampsia homozygous for methylenetetrahydrofolate reductase C677T and controls (72 vs. 10%, p ‹ 0.008 and 63.6 vs. 10%, p ‹ 0.05, respectively). Patients with two or more abnormal tests, including homozygousity for the C677T allele had an increased risk of preeclampsia than those with one or no abnormal test (OR: 3.15; CI: 1.1-9.02).
Conclusion: Methylenetetrahydrofolate reductase C677T has a high allelic prevalence and is associated with markers of thrombosis and endothelial activation in Mexican women with preeclampsia.

REFERENCES

1. Romero-Gutierrez G, Velasquez-Maldonado HA, Mendez-Sashida P, Horna-Lopez A, et al. [Placental histopathological changes in gestational hypertension]. Ginecol Obstet Mex 2008;76:673-678.

2. Kupferminc MJ, Eldor A, Steinman N, Many A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999;340:9-13.

3. Lindqvist PG, Svensson P, Dahlback B. Activated protein C resistance – in the absence of factor V Leiden – and pregnancy. J Thromb Haemost 2006;4:361-366.

4. Maynard SE, Min JY, Merchan J, Lim KH, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649-658.

5. Ruiz-Arguelles GJ, Garces-Eisele J, Reyes-Nunez V, Ramirez-Cisneros FJ. Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos. Am J Hematol 2001;66:28-31.

6. Perales Davila J, Martinez de Villarreal LE, Triana Saldana H, Saldívar Rodríguez D, et al. [Folic acid levels, homocysteine and polymorphism of methylenetetrahydrofolate reductase enzyme (MTHFR) in patients with pre-eclampsia and eclampsia]. Ginecol Obstet Mex 2001;69:6-11.

7. Yamada K, Chen Z, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci USA 2001;98:14853-14858.

8. Torres-Sanchez L, Chen J, Diaz-Sanchez Y, Palomeque C, et al. Dietary and genetic determinants of homocysteine levels among Mexican women of reproductive age. Eur J Clin Nutr 2006;60:691-697.

9. Undas A, Williams EB, Butenas S, Orfeo T, Mann KG. Homocysteine inhibits inactivation of factor Va by activated protein C. J Biol Chem 2001;276:4389-4397.

10. Baptista-Gonzalez HA, Rosenfeld-Mann F, Saavedra-Trejo MR, Castro-Lopez JL, Penuela-Olaya MA. [Changes in the thrombophilic status in patients with pre-eclampsia]. Ginecol Obstet Mex 1999;67:176-182.

11. Upchurch GR Jr, Welch GN, Fabian AJ, Freedman JE, et al. Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997;272:17012-17017.

12. Ollivier V, Chabbat J, Herbert JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves thrombin and factor Xa. Arterioscler Thromb Vasc Biol 2000;20:1374-1381.