跳至主要内容

Relationship between Methylenetetrahydrofolate Reductase (C677T), Factor V Leiden (G1691A), Prothrombin Mutation (G20210A) and Severe Preeclampsia in a Brazilian Population

Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=48153#.VEXyNFfHRK0

Objectives: To better understand the etiologic factors that can influence preeclampsia, we inves- tigated hereditary factors for thrombosis, FV Leiden, F II 20210A mutation and the polymorphism C677T of the MTHFR, as singly and as in association, in a group of women from Ceará state-Northeast Brazil with severe preeclampsia. Material and Methods: We conducted a case-control study. 101 cases of severe preeclampsia were recruited from School Maternity Assis Chateaubriand, a reference Maternity of State of Ceará, Brazil, from December 2009 to December 2010. For clinical correlations, women were interrogated about fetal low weight (less than2500 grams) and fetal loss in previous pregnancies. Low weight, fetal loss and necessity of neonatal intensive care unit (neonatal ICU) related to current pregnancy were registered. 245 healthy voluntary women were recruited from the blood bank donors to verify the frequency of FV Leiden, FII and MTHFR as a control group. The study was approved by the Committee on Ethics in Human Research of Maternidade Escola Assis Chateubriand and all individuals gave their informed consent to participate in the study. Standard veinipuncture, with EDTA as anticoagulant, was used to collect blood samples. Genomic DNA was extracted, soon after, using a salting out method. Agarose gel electrophoresis with ethidium bromide staining was performed to ensure the quality of DNA extraction. Results: The frequencies of FV Leiden and FII mutation carrier were 0.99% (1/101) for both factors in the preeclampsia patients and 1.86% (4/214) and 0.93% (2/214), respectively, in control group. All mutates were heterozygous and concomitance of both mutations was not found. The genotype distribution of the MTHFR C677T in the patients and controls frequencies was in Hardy-Weinberg equilibrium (p ≤ 0.05). No statistical difference was observed between cases and controls in MTHFR genotypes or alleles. Conclusions: The FV Leiden, FII G20210A mutation and MTHFR C677T were not risks for preeclampsia development. FV Leiden and FII G20210A mutations had low frequency in the population studied, which may justify the absence of association.
Cite this paper
Freire, T. , Holanda, G. , Costa, D. , Sampaio, Z. , Feitosa, F. and Rabenhorst, S. (2014) Relationship between Methylenetetrahydrofolate Reductase (C677T), Factor V Leiden (G1691A), Prothrombin Mutation (G20210A) and Severe Preeclampsia in a Brazilian Population. Open Journal of Obstetrics and Gynecology, 4, 628-635. doi: 10.4236/ojog.2014.410087. 
 

[1] Steegers, E.A., von Dadelszen, P., Duvekot, J.J. and Pijnenborg, R. (2010) Pre-Eclampsia. Lancet, 376, 631-644. http://dx.doi.org/10.1016/S0140-6736(10)60279-6
[2] de Maat, M.P., de Groot, C.J. (2011) Thrombophilia and Pre-Eclampsia. Seminars in Thrombosis and Hemostasis, 37, 106-110. http://dx.doi.org/10.1055/s-0030-1270335
[3] Deveer, R., Engin-Ustun, Y., Akbaba, E., Halisdemir, B., Cakar, E., Danisman, N., Mollamahmutoglu, L., Yesilyurt, A. and Candemir, Z. (2012) Association between Pre-Eclampsia and Inherited Thrombophilias. Fetal Pediatric Pathology, 32, 213-217.
[4] Vucic, N., Frleta, M., Petrovic, D. and Ostojic, V. (2009) Thrombophilia, Preeclampsia and Other Pregnancy Complications. Acta Medica Croatica, 63, 297-305.
[5] Rath, W. (2011) Pre-Eclampsia and Inherited Thrombophilia: A Reappraisal. Seminars in Thrombosis and Hemostasis, 37, 118-124. http://dx.doi.org/10.1055/s-0030-1270337
[6] Ahn, H., Park, J., Gilman-Sachs, A. and Kwak-Kim, J. (2011) Immunologic Characteristics of Preeclampsia, a Comprehensive Review. American Journal of Reproductive Immunology, 65, 377-394.
http://dx.doi.org/10.1111/j.1600-0897.2010.00913.x
[7] Rojas, J.C., Luna, M., Rangel-Nava, H., Banos, D. and Collados, M.T. (2010) Genetic Thrombophilia and Markers of Endothelial Activation in Patients with Preeclampsia. Ginecología y Obstetricia de México, 78, 401-409.
[8] Best, L.G., Dorsam, S.T., Nadeau, M., Burd, L. and Anderson, C.M. (2009) Genetic Thrombophilia Variants and Risk for Preeclampsia among American Indians. Hypertension in Pregnancy, 28, 85-94.
http://dx.doi.org/10.1080/10641950802419887
[9] Kjellberg, U., van Rooijen, M., Bremme, K. and Hellgren, M. (2010) Factor V Leiden Mutationand Pregnancy-Related Complications. American Journal of Obstetrics Gynecology, 203, 469.e1-e8.
[10] Almawi, W.Y., Keleshian, S.H., Borgi, L., Fawaz, N.A., Abboud, N., Mtiraoui, N. and Mahjoub, T. (2005) Varied Prevalence of Factor V G1691A (Leiden) and Prothrombin G20210A Single Nucleotide Polymorphisms among Arabs. Journal of Thrombosis and Thrombolysis, 20, 163-168.
http://dx.doi.org/10.1007/s11239-005-3550-4
[11] Franco, R.F., Trip, M.D., Ten Cate, H., et al. (1999) The 20210 G A Mutation in the 3’-Untranslated Region of the Prothrombin Gene and the Risk for Arterial Thrombotic Disease. British Journal of Haematology, 104, 50-54. http://dx.doi.org/10.1046/j.1365-2141.1999.01149.x
[12] de Vries JI, Kist WJ, Hague WM. (2009) Confounded Thrombophilia Studies in Preeclampsia. American Journal of Obstetrics Gynecology, 201, e11-e12. http://dx.doi.org/10.1016/j.ajog.2009.05.017
[13] Calvert, H. (1999) An Overview of Folate Metabolism: Features Relevant to the Action and Toxicities of Antifolate Anticancer Agents. Seminars in Oncology, 26, 3-10.
[14] Carmel, R., Green, R., Rosenblatt, D.S. and Watkins, D. (2003) Update on Cobalamin, Folate, and Homocysteine. Hematology-American Society of Hematology Education Program, 2003, 62-81.
http://dx.doi.org/10.1182/asheducation-2003.1.62
[15] Hoffmann, E., Hedlund, E., Perin, T. and Lyndrup, J. (2012) Is Thrombophilia a Risk Factor for Placenta-Mediated Pregnancy Complications? Archives of Gynecology and Obstetrics, 286, 585-589.
http://dx.doi.org/10.1007/s00404-012-2342-2
[16] Benedetto, C., Marozio, L., Tavella, A.M., Salton, L., Grivon, S. and Di Giampaolo, F. (2010) Coagulation Disorders in Pregnancy: Acquired and Inherited Thrombophilias. Annals of the New York Academy of Sciences, 1205, 106-117. http://dx.doi.org/10.1111/j.1749-6632.2010.05674.x
[17] Kahn, S.R., Platt, R., McNamara, H., Rozen, R., Chen, M.F., Genest, Jr., J., Goulet, L., Lydon, J., Seguin, L., Dassa, C., Masse, A., Asselin, G., Benjamin, A., Miner, L., Ghanem, A. and Kramer, M.S. (2009) Inherited Thrombophilia and Preeclampsia within a Multicenter Cohort: The Montreal Preeclampsia Study. American Journal of Obstetrics Gynecology, 200, 151.e1-e9 Discussion
[18] Kupferminc, M.J., Fait, G., Many, A., Gordon, D., Eldor, A. and Lessing, J.B. (2000) Severe Pre-Eclampsia and High Frequency on Genetic Thrombophilic Mutations. Obstetrics Gynecology, 96, 45-49.
http://dx.doi.org/10.1016/S0029-7844(00)00861-9
[19] ACOG Committee on Practice Bulletins—Obstetrics (2002) ACOG Practice Bulletin. Diagnosis and Management of Preeclampsia and Eclampsia. Obstetrics Gynecology, 77, 67-75.
[20] Bertina, R.M., Koeleman, B.P.C., Koster, T., Rosendaal, F.R., Dirven, R.J., de Ronde, H., van der Velden, P.A. and Reitsma, P.H. (1994) Mutation in Blood Coagulation Factor V Associated with Resistance to Activated Protein C. Nature, 369, 64-67. http://dx.doi.org/10.1038/369064a0
[21] Poort, S.R., Rosendaal, F.R. and Reitsma, P.H. (1996) A Common Genetic Variation in the 3’-Untranslated Region of the Prothrombin Gene Is Associated with Elevated Plasma Prothrombin Levels and an Increase in Venous Thrombosis. Blood, 88, 3698-3703.
[22] Frosst, P., Blom, H.J., Milos, R., Goyette, P., Sheppard, C.A., Matthews, R.G., Boers, G.J., den Heijer, M., Kluijtmans, L.A., van den Heuvel, L.P., et al. (1995) A Candidate Genetic Risk Factor for Vascular Disease: A Common Mutation in Methylenetetrahydrofolate Reductase. Nature, 10, 111-113.
[23] Dalmaz, C.A., Santos, K.G., Bottom, M.R., Tedoldi, C.L. and Roisenberg, I. (2006) Relationship between Polymorphisms in Thrombophilic Genes and Preeclampsia in a Brazilian population. Blood Cells, Molecules, and Diseases, 37, 107-110. http://dx.doi.org/10.1016/j.bcmd.2006.07.005
[24] O’Shaughnessy, K.M., Fu, B., Ferraro, F., Lewis, I., Downing, S. and Morris, N.H. (1999) Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Gene Variants in an East Anglian Preeclampsia Cohort. Hypertension, 33, 1338-1341. http://dx.doi.org/10.1161/01.HYP.33.6.1338
[25] De Groot, C.J.M., Bloemenkamp, K.W.M., Duvekot, E.L., Helmerhorst, F.M., Bertina, R.M., Van Der Meer, F., De Ronde, H., Oei, S.G., Kanhai, H.H.H. and Rosendaal, F.R. (1999) Preeclampsia and Genetic Risk Factors for Thrombosis: A Case Control Study. American Journal of Obstetrics & Gynecology, 181, 975-980. http://dx.doi.org/10.1016/S0002-9378(99)70335-2
[26] Mello, G., Parrett, E., Mario, L., Pizzi, C., Lojacono, A., Frusca,T., Facchinetti, F. and Benedetto, C. (2007) Thrombophilia Is Significantly Associated with Severe Preeclampsia Results of a Large-Scale, Case-Controlled Study. Hypertension, 46, 1270-1274.
[27] Kupferminc, M.J., Eldor, A., Stemman, N., Many, A., Bar-Arn, A., Jaffa, A., et al. (1999) Increased Frequency of Genetic Thrombophilia in Women with Complications of Pregnancy. The New England Journal of Medicine, 340, 9-13. http://dx.doi.org/10.1056/NEJM199901073400102
[28] Figueiro Filho, E.A., Oliveira, V.M., Coelho, L.R. and Brenda, I. (2012) Serum Markers of Inherited Trombophilia and Antiphospholipid Antibodies in Pregnant Women with Previous History of Severe Pre-Eclampsia. Revista Brasileira de Ginecologia e Obstetrícia, 34, 40-46.
[29] Infante-Rivard, C., Rivard, G.E., Yotov, W.V., Genin, E., Guiguet, M., Weinberg, C., Gauthier, R. and Feoli-Fonseca, J.C. (2002) Absence of Association of Thrombophilia Polymorphisms with Intrauterine Growth Restriction. The New England Journal of Medicine, 347, 19-25.
http://dx.doi.org/10.1056/NEJM200207043470105
[30] Martinelli, P., Grandone, E., Colaizzo, D., et al. (2001) Familial Thrombophilia and the Occurrence of Fetal Growth Restriction. Haematologica, 86, 428-431.
[31] Kalhan, S.C. (2013) One-Carbon Metabolism, Fetal Growth and Long-Term Consequences. Nestlé Nutrition Workshop Series, 74, 127-38. http://dx.doi.org/10.1159/000348459
[32] Nazki, F.H., Sameer, A.S. and Ganaie, B.A. (2014) Folate: Metabolism, Genes, Polymorphisms and the Associated Diseases. Gene, 533, 11-20. http://dx.doi.org/10.1016/j.gene.2013.09.063
[33] Guéant, J.L., Namour, F., Guéant-Rodriguez, R.M. and Daval, J.L. (2013) Folate and Fetal Programming: A Play in Epigenomics? Trends in Endocrinology and Metabolism, 24, 279-289.
http://dx.doi.org/10.1016/j.tem.2013.01.010
[34] Black, R.E., Victora, C.G., Walker, S.P., Bhutta, Z.A., Christian, P., de Onis, M., Ezzati, M., Grantham-McGregor, S., Katz, J., Martorell, R., Uauy, R., Maternal and Child Nutrition Study Group (2013) Maternal and Child Undernutrition and Overweight in Low-Income and Middle-Income Countries. Lancet, 382, 427-451. http://dx.doi.org/10.1016/S0140-6736(13)60937-X
[35] van Uitert, E.M. and Steegers-Theunissen, R.P. (2013) Influence of Maternal Folate Status on Human Fetal Growth Parameters. Molecular Nutrition Food Research, 57, 582-595.
http://dx.doi.org/10.1002/mnfr.201200084                      eww141021lx
标签：

评论

发表评论

此博客中的热门博文

A Comparison of Methods Used to Determine the Oleic/Linoleic Acid Ratio in Cultivated Peanut (Arachis hypogaea L.)

Cultivated peanut ( Arachis hypogaea L.) is an important oil and food crop. It is also a cheap source of protein, a good source of essential vitamins and minerals, and a component of many food products. The fatty acid composition of peanuts has become increasingly important with the realization that oleic acid content significantly affects the development of rancidity. And oil content of peanuts significantly affects flavor and shelf-life. Early generation screening of breeding lines for high oleic acid content greatly increases the efficiency of developing new peanut varieties. The objective of this study was to compare the accuracy of methods used to classify individual peanut seed as high oleic or not high oleic. Three hundred and seventy-four (374) seeds, spanning twenty-three (23) genotypes varying in oil composition (i.e. high oleic (H) or normal/not high oleic (NH) inclusive of all four peanut market-types (runner, Spanish, Valencia and Virginia), were individually tested ...
发表评论
阅读全文

Location Optimization of a Coal Power Plant to Balance Costs against Plant’s Emission Exposure

Fuel and its delivery cost comprise the biggest expense in coal power plant operations. Delivery of electricity from generation to consumers requires investment in power lines and transmission grids. Placing a coal power plant or multiple power plants near dense population centers can lower transmission costs. If a coalmine is nearby, transportation costs can also be reduced. However, emissions from coal plants play a key role in worsening health crises in many countries. And coal upon combustion produces CO 2 , SO 2 , NO x , CO, Metallic and Particle Matter (PM10 & PM2.5). The presence of these chemical compounds in the atmosphere in close vicinity to humans, livestock, and agriculture carries detrimental health consequences. The goal of the research was to develop a methodology to minimize the public’s exposure to harmful emissions from coal power plants while maintaining minimal operational costs related to electric distribution losses and coal logistics. The objective was...
发表评论
阅读全文

Evaluation of the Safety and Efficacy of Continuous Use of a Home-Use High-Frequency Facial Treatment Appliance

At present, many home-use beauty devices are available in the market. In particular, many products developed for facial treatment use light, e.g., a flash lamp or a light-emitting diode (LED). In this study, the safety of 4 weeks’ continuous use of NEWA TM , a high-frequency facial treatment appliance, every alternate day at home was verified, and its efficacy was evaluated in Japanese individuals with healthy skin aged 30 years or older who complained of sagging of the facial skin.  Transepidermal water loss (TEWL), melanin levels, erythema levels, sebum secretion levels, skin color changes and wrinkle improvement in the facial skin were measured before the appliance began to be used (study baseline), at 2 and 4 weeks after it had begun to be used, and at 2 weeks after completion of the 4-week treatment period (6 weeks from the study baseline). In addition, data obtained by subjective evaluation by the subjects themselves on a visual analog scale (VAS) were also analyzed. Fur...
发表评论
阅读全文