Información de la revista
Vol. 60. Núm. 3.
Páginas 215-221 (marzo 2004)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 60. Núm. 3.
Páginas 215-221 (marzo 2004)
Acceso a texto completo
Influencia de factores bioquímicos y genéticos en las concentraciones de homocisteína
Influence of biochemical and genetic factors on homocysteine concentrations
Visitas
12268
J.I. Gutiérrez Revillaa,
Autor para correspondencia
joseignaciogutierrez@redfarma.org

Correspondencia: Servicio de Bioquímica Clínica. Sección de Genética. Hospital Universitario Miguel Servet. P.° Isabel La Católica, 1 y 3. 50009 Zaragoza. España.
, F. Pérez Hernándezb, M. Tamparillas Salvadora, M.aT. Calvo Martína
a Servicio de Bioquímica Clínica. Sección de Genética. Hospital Universitario Miguel Servet. Zaragoza
b Farmacéutica de Atención Primaria. Gerencia Santander-Laredo. Santander. España
Este artículo ha recibido
Información del artículo
Antecedentes

En varios estudios se ha analizado la asociación entre el genotipo del gen metilentetrahidrofolato reductasa (MTHFR) y las concentraciones de homocisteína plasmática, pero muy pocos estudios se han realizado en niños.

Objetivo

Determinar la concentración plasmática de homocisteína total, ácido fólico, folato intraeritrocitario (FCR) y vitamina B12 en un grupo de niños sanos y ver su posible relación con el genotipo MTHFR.

Sujetos y métodos

Formaron parte del estudio 83 participantes (45 chicos y 38 chicas) de edad comprendida entre 1 semana y 18 años. Las muestras de plasma y sangre completa se almacenaron a –80 °C para su posterior determinación de los parámetros bioquímicos y moleculares. La determinación de homocisteína total se realizó mediante ensayo de inmunofluorescencia polarizada; mientras que la concentración sérica de ácido fólico, folato intraeritrocitario y vitamina B12 se determinó mediante inmunoanálisis electroquimioluminiscente. El análisis molecular se realizó mediante reacción en cadena de la polimerasa (PCR), y posterior digestión enzimática, del ADN obtenido de las muestras de sangre.

Resultados

Las concentraciones plasmáticas de homocisteína se correlacionaron negativamente con las de ácido fólico, vitamina B12 y FCR, pero positivamente con la edad (p < 0,005). Se ha encontrado una interacción entre la edad-genotipo MTHFR y las concentraciones de ácido fólico, vitamina B12 y FCR, pero no con las concentraciones de homocisteína.

Conclusiones

Nuestras observaciones sugieren que la concentración de homocisteína en la población pediátrica sana está más influida por factores bioquímicos como el ácido fólico, que genéticos.

Palabras clave:
Homocisteína
Metilentetrahidrofolato reductasa
Ácido fólico
Vitamina B12
Folato intraeritrocitario
Background

Several studies have examined the association between the methylenetetrahydrofolate reductase (MTHFR) genotype and plasma homocysteine concentrations in adults but few studies have been performed in children.

Objective

To determine plasma concentrations of total homocysteine, folate, vitamin B12, and red cell folate in a group of healthy children and to determine their possible relationship with the MTHFR genotype.

Subjects and methods

Eighty-three subjects (45 boys and 38 girls), aged between 1 week and 18 years, were included in the study. Plasma and whole blood samples were stored at –80 °C for biochemical and molecular analysis. Plasma total homocysteine was determined by fluorescence polarization immunoassay. Serum concentrations of folate, vitamin B12, and red cell folate were measured by electrochemiluminescence immunoassay. Genotypic analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from blood leukocytes.

Results

Plasma homocysteine concentrations were negatively correlated with folate, vitamin B12, and red cell folate but were positively correlated with age (p < 0.005). There was an association between age-MTHFR genotype and folic acid, vitamin B12, and red cell folate, but not with homocysteine concentrations.

Conclusions

Our results suggest that in a healthy pediatric population, homocysteine concentrations are determined by biochemical factors, such as folic acid, more than by genetic factors.

Key words:
Homocysteine
Methylenetetrahydrofolate reductase
Folic acid
Vitamin B12
Red cell folate
El Texto completo está disponible en PDF
Bibliografía
[1]
E.L. López-Quesada, M.A. Vilaseca, S. González.
Homocysteine and pregnancy.
Med Clin (Barc), 115 (2000), pp. 352-356
[2]
A. De Bree, W.M.M. Verschuren, A.L. Bjorke-Monsen, N.M.J. Van der Put, S.G. Heil, F.J.M. Trijbels, et al.
Effect of the methylenetetrahydrofolate reductasa 677C-T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample.
Am J Clin Nutr, 77 (2003), pp. 687-693
[3]
C. Mainou, N. García, M.A. Vilaseca, I. Ferrer, J.F. Meco, A. Mainou, et al.
Hiperhomocistinemia y polimorfismo 677C-T de la 5,10-metilenotetrahidrofolato reductasa en hijos de pacientes con enfermedad coronaria prematura.
An Esp Pediatr, 56 (2002), pp. 402-408
[4]
E.E. Delvin, R. Rozen, A. Merouani, J. Genest, M. Lambert.
Influence of methylenetetrahydrofolate reductasa genotype, age, vitamin B12, and folate status on plasma homocysteine in children.
Am J Clin Nutr, 72 (2000), pp. 1469-1473
[5]
A.J. Gonzalez Ordóñez, J.M. Medina Rodríguez, C.R. Fernández Álvarez, J. Sánchez García, J.M. Fernández Carreira, M.V. Álvarez Martínez, et al.
Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: Relationship between response and the C677T methylenetetrahydrofolate reductase (MTHFR) genotype.
Med Clin (Barc), 114 (2000), pp. 7-12
[6]
P. Goyette, J.S. Summer, R. Milos, A.M.V. Duncan, D.S. Rosenblatt, R.G. Mattews, et al.
Human methylenetetrahydrofolate reductase: Isolation of cDNA, mapping and mutation identification.
Nat Genet, 7 (1994), pp. 195-200
[7]
N.M.J. Van der Put, R.P.M. Steegers-Theunissen, P. Frosst, F.J.M. Trijbeis, T.K.A.B. Eskes, L.P. Van den Heuvet, et al.
Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida.
Lancet, 21 (1995), pp. 1070-1071
[8]
P. Frosst, H.J. Blom, R. Milos, P. Goyette, C.A. Sheppard, R.G. Matthews, et al.
A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase.
Nat Genet, 10 (1995), pp. 111-113
[9]
R. De Franchis, A. Buoninconti, C. Mandato, A. Pepe, M.P. Sperandeo, R. Del Gado, et al.
J Med Genet, 35 (1998), pp. 1009-1013
[10]
C. Papapetrou, S.A. Lynch, S. Burn, W.H. Edwards.
Methylentetrahydrofolate reductase and neural tube defects.
Lancet, 6 (1996), pp. 58
[11]
L.A.J. Kluijtmans, L.P.W.J. Van den Heuvel, G.H.J. Boers, P. Frosst, E.M.B. Stevens, B.A. Van Oost, et al.
Molecular genetic analysis in mild hyperhomocysteinemia: A common mutation in the methylenetetrahydrofolate reductase is a genetic risk factor for cardiovascular disease.
Am J Hum Genet, 58 (1996), pp. 35-41
[12]
D.L. Harmon, J.V. Woodside, J.W.G. Yarnell, D. McMaster, I.S. Young, E.E. McCrum, et al.
The common “thermolabile” variant of methylene tetrahydrofolate reductase is a mayor determinant of mild hyperhomocysteinemia.
Q J Med, 89 (1996), pp. 571-577
[13]
A.M. Molloy, S. Daly, J.L. Mills, P.N. Kirke, A.S. Whitehead, D. Ramsbottom, et al.
Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: Implications for folate intake recommendations.
Lancet, 349 (1997), pp. 1591-1593
[14]
J. Ma, M.J. Stampfer, C.H. Hennekens, P. Frosst, J. Selhub, J. Horsford, et al.
Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of miocardial infarction in US physicians.
Circulation, 94 (1996), pp. 2410-2416
[15]
B. Shannon, S. Gnanasampanthan, J. Beilby, B. Lacopetta.
A polymorphism in the methylenetetrahyfrofolate reductasa gene predisposes to colorectal cancers with microsatellite instability.
Gut, 50 (2002), pp. 520-524
[16]
J. Hung, J.P. Beilby, M.W. Knuiman, M. Divitini.
Folate and vitamin B12 and risk of fatal cardiovascular disease: Cohort study from Busselton. Western Australia.
BMJ, 326 (2003), pp. 131-137
[17]
L.A.J. Kluijtmans, J.J.P. Kastelein, J. Lindemans, G.H. Boers, S.G. Heil, A.V. Bruschke, et al.
Thermolabile methylenetetrahydrofolate reductase in coronary artery disease.
Circulation, 96 (1999), pp. 2573-2577
[18]
L. Brattstrom, D.E.L. Wilken, J. Ohrvik, L. Brudin.
Common methylenetetrahydrofolate reductasa mutation leads to hyperhomocysteinemia but not vascular disease. The result of a meta-analysis.
Circulation, 98 (1998), pp. 2520-2526
[19]
C. De Late, J.C. Wautrecht, D. Brasseur, M. Dramaix, J.M. Boeynaems, J. Decuyper, et al.
Plasma homocysteine concentrations in a Belgian school-age population.
Am J Clin Nutr, 69 (1999), pp. 968-972
[20]
M.A. Vilaseca, D. Moyano, I. Ferrer, R. Artuch.
Total homocysteine in pediatric patients.
Clin Chem, 43 (1997), pp. 690-692
[21]
S.K. Osganian, M.J. Stampfer, D. Spiegelman, E. Rimm, J.A. Cutler, H.A. Feldman, et al.
Distribution of and factors associated with serum homocysteine levels in children. Child and adolescent trial for cardiovascular health.
JAMA, 281 (1999), pp. 1189-1196
[22]
K.L. Tucker, J. Selhub, P.W.F. Wilson, J.H. Rosenberg.
Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study.
J Nutr, 126 (1996), pp. 3025-3031
[23]
K.J. Greenlund, S.R. Srinivasan, J.H. Xu, E. Dalferes, L. Myers, A. Pickoff, et al.
Plasma homocysteine distribution and its association with parental history of coronary artery disease in black and white children.
Circulation, 99 (1999), pp. 2144-2149
[24]
R.S. Gibson.
Nutritional assessment. A laboratory manual.
Oxford University Press, (1993),
[25]
C.A. Lewis, N. Pancharuniti, H.E. Sauberlicg.
Plasma folate adequacy as determined by homocysteine level.
Ann N Y Acad Sci, 669 (1998), pp. 360-362
[26]
E. Muñoz-Morán, J.L. Diéguez-Lucena, N. Fernández-Arcas, S. Perán-Mesa, A. Reyes-Engel.
Genetic selection and folate intake during pregnancy.
Lancet, 352 (1998), pp. 1120-1121
[27]
R.F. Franco, A.G. Araujo, J.F. Guerreiro, J. Elion, M.A. Zago.
Analysis of the C677T mutation of the methylenetetrahydrofolate reductasa gene in different ethnic groups.
Thromb Haemost, 79 (1998), pp. 119-121
[28]
M.C. Koch, K. Stegmann, A. Ziegler, B. Schröter, A. Ermert.
Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population.
Eur J Pediatr, 157 (1998), pp. 487-492
[29]
C. Papapetrou, S.A. Lynch, S. Burn, W.H. Edwards.
Methylentetrahydrofolate reductase and neural tube defects.
Lancet, 6 (1996), pp. 58
[30]
E. Mornet, F. Muller, A. Lenvoise-Furet, A.L. Delezoide, J.Y. Col, B. Simon-Bouy, et al.
Screening of the C677T mutation on the methylenetetrahydrololate reductase gene in French patients with neural tube defects.
Hum Genet, 100 (1997), pp. 512-514
[31]
K. Boduroglu, M. Alikasiflogu, B. Anar, E. Tuncbilek.
677CT mutation on the methylenetetrahydrololate reductase gene is not a risk factor for neural tube defects in Turkey.
Arch Dis Child Fetal Neonatal, 78 (1998), pp. 235
[32]
V.V. Balasa, R.A. Gruppo, C.J. Glueck, D. Stroop, A. Becker, A. Pillow, et al.
The relationship of mutations in the MTHFR, prothrombin, and PAI-1 genes to plasma levels of homocysteine, prothrombin and PAI-1 in children and adults.
Thromb Haemost, 81 (1999), pp. 739-744
[33]
C.J. Bates, M.A. Mansoor, J. Gregory, K. Pentiev, A. Prentice.
Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutritional Survey of young people aged 4-18 years, and a comparison with survey of people aged 65 years and over.
Br J Nutr, 87 (2002), pp. 71-79
Copyright © 2004. Asociación Española de Pediatría
Descargar PDF
Idiomas
Anales de Pediatría
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?