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Vol. 56. Núm. 5.
Páginas 402-408 (mayo 2002)
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Vol. 56. Núm. 5.
Páginas 402-408 (mayo 2002)
Acceso a texto completo
Hiperhomocistinemia y polimorfismo 677C → T de la 5,10-metilenotetrahidrofolato reductasa en hijos de pacientes con enfermedad coronaria prematura
Hyperhomocystinemia and 677C → T methylenetetrahydrofolate reductase polymorphism as a cardiovascular risk factor in childhood
Visitas
8358
C. Mainou Cida,
Autor para correspondencia
mainou@medicina.ub.es

Correspondencia: Servicio de Pediatría. Hospital Sant Joan de Déu. P.° Sant Joan de Déu, 2. 08950 Esplugues. Barcelona
, N. García Giraltb, M.aA. Vilaseca Buscàc, I. Ferrer Codinac, José F. Meco Lópezd, A. Mainou Pintóa, X. Pintó Salad, D. Grinberg Vaismanb, S. Balcells Comasb
a Servicio de Pediatría. Hospital Universitario Sant Joan de Déu. Barcelona.
b Departamento de Genética. Facultad de Biología. Universidad de Barcelona.
c Servicio de Bioquímica. Hospital Universitario Sant Joan de Déu. Barcelona.
d Unidad de Aterosclerosis. CSUB.
Este artículo ha recibido
Información del artículo
Antecedentes

Los factores relacionados con la hiperhomocistinemia en la población pediátrica con historia de enfermedad coronaria prematura (ECP) no son bien conocidos.

Objetivos

Evaluar la posible asociación entre la homocisteína plasmática, las vitaminas B (folatos, B12 B6) y el polimorfismo 677C → T de la enzima 5,10-metilenotetrahidrofolato reductasa (MTHFR) en un grupo de hijos de progenitores on ECP.

Métodos

Estudio transversal analítico de 80 hijos (5–18 años) de progenitores con ECP comparando sus valores con los de referencia de edades similares. homocisteína total y vitamina B6: cromatografía líquida de alta resolución (HPLC) con detección fluorimétrica; folato y vitamina B12: radioinmunoanálisis; polimorfismo 677C → T de la MTHFR: amplificación por reacción en cadena de la polimerasa (PCR) y digestión con Hinfl. Estudio estadístico (SPSS, versión 10.0). Comparaciones: U de Mann-Witney y chi cuadrado; correlaciones de Spearman.

Resultados

Los valores de homocisteína total de los hijos de progenitores con ECP mayores de 10 años fueron significativamente superiores (p < 0,001) a los valores de referencia, mientras que los de vitamina B12 fueron inferiores (p = 0,015), aunque no los de folato y vitamina B6. Se observó una correlación negativa (p < 0,0001) entre la homocisteína total y el folato (r = -0,47) y la vitamina B12 (r = -0,51). El 80 % de los hijos con el genotipo TT de la MTHFR presentaron hiperhomocistinemia. Los valores subóptimos de vitaminas mostraron también una asociación el genotipo TT.

Conclusiones

La hiperhomocistinemia de los hijos de pacientes con ECP de nuestro medio se asocian al genotipo TT de la MTHFR y a unas concentraciones bajas de folato. La posibilidad de corregir la hiperhomocistinemia mediante suplementación vitamínica sugiere el interés del estudio familiar de homocisteína en la ECP.

Palabras clave:
Homocisteína
MTHFR Folatos
Vitaminas B12 y B6
Enfermedad coronaria prematura
Niños
Background

Factors related to hyperhomocystinemia in the pediatric population of our geographical area with a parental history of premature coronary disease (PCD) are not well known.

Objectives

To evaluate the possible association between plasma total homocysteine (tHcy), the B vitamins involved in its metabolism (folate, vitamin Bl2 and B6), and 677C → T polymorphism of methylenetetrahydrofolate reductase (MTHFR) in a group of children with a parental history of PCD.

Methods

A cross-sectional analytical study of 80 children (aged 5–18 years old) with a parental history of PCD was performed. Values found in these children were compared with reference values for similar age groups. Plasma tHcy and vitamin B6 were evaluated by high-performance liquid chromatography with fluorometric detection. Folate and vitamin B12 concentrations were determined by radioimmunoassay. Detection of 677C → T polymorphism of MTHFR was performed using polymerase chain reaction amplification and Hinfl digestion. Statistical analysis was performed using the SPSS program, version 10.0. Concentrations of tHcy and vitamins were compared using the Mann-Whitney U-test and Spearman’s correlation coefficient. The association between phenotype, hyperhomocystinemia and low vitamin concentrations was analyzed using the chi-squared test.

Results

Plasma tHcy values in the children aged more than 10 years with a parental history of PCD were significantly higher (p < 0.001) than the reference values. Vitamin B12 levels were significantly lower (p = 0.015), but neither folate nor vitamin B6 levels differed from the reference values. A negative correlation (p < 0.0001) was observed between tHcy and folate (r = -0.47) and between tHcy and vitamin B12 levels (r = -0.51). Eighty percent of the children with the TT genotype of MTHFR showed hyperhomocystinemia. Suboptimal vitamin B levels were also associated with the TT genotype of MTHFR.

Conclusions

Hyperhomocystinemia detected in children with a parental history of PCD is associated with the TT genotype of MTHFR and with low folate levels. Because hyperhomocystinemia can be corrected by vitamin B supplementation, tHcy determination is recommended in the offspring of patients with PCD.

Keywords:
Homocysteine
Methylenetetrahydrofolate reductase (MTHFR) Folate
Vitamin B12 y B6
Premature coronary disease
Children
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Bibliografía
[1.]
National Cholesterol Education Program (NCEP)..
Report of the expert panel on blood cholesterol levels in children and adolescents.
Pediatrics, 89 (1992), pp. 525-584
[2.]
C. Mainou, M.E. May, M.T. Palá, I. Ferrer, M.A. Vilaseca.
Factores de riesgo cardiovascular en la infancia. Nuevas perspectivas.
Rev Esp Pediatr, 53 (1997), pp. 1-5
[3.]
R.M. Ortega.
Utilidad y riesgos del seguimiento de pautas dietéticas encaminadas a disminuir el riesgo cardiovascular, desde la infancia.
An Esp Pediatr, 50 (1999), pp. 576-580
[4.]
M. Rasanen, H. Niinikoski, S. Keskinen, J. Tuominen, O. Simell, J. Viikari, et al.
Nutrition knowledge and food intake of seven-year-old children in an atherosclerosis prevention project with onset in infancy: The impact of child-targeted nutrition counselling given to the parents.
Eur J Clin Nutr, 55 (2001), pp. 260-267
[5.]
O. Nygard, H. Refsum, P.M. Ueland, S.E. Vollset.
Major lifestyle determinants of plasma total homocysteine distribution: The Hordaland Homocysteine Study.
Am J Clin Nutr, 67 (1998), pp. 263-270
[6.]
J. Selhub, P.F. Jacques, I.H. Rosenberg, G. Rogers, B.A. Bowman, E.W. Gunter, et al.
Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): Population reference ranges and contribution of vitamin status to high serum concentrations.
Ann Intern Med, 131 (1999), pp. 331-339
[7.]
C.J. Boushey, S.A. Beresford, G.S. Omenn, A.G. Motulsky.
A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.
Jama, 274 (1995), pp. 1049-1057
[8.]
S.H. Mudd, H.L. Levy, F. Skovby.
Disorders of transsulfuration.
The metabolic and molecular bases of inherited disease.7th ed. Vol 1, pp. 3111-3128
[9.]
K.S. McCully.
Vascular pathology of homocysteinemia: Implications for the pathogenesis of arteriosclerosis.
Am J Pathol, 56 (1969), pp. 111-128
[10.]
D.E.L. Wilken, B. Wilken.
The pathogenesis of coronary artery disease. A possible role for methionine metabolism.
J Clin Invest, 57 (1976), pp. 1079-1082
[11.]
P.M. Ueland, H. Refsum, S.A. Beresford, S.E. Vollset.
The controversy over homocysteine and cardiovascular risk.
Am J Clin Nutr, 72 (2000), pp. 324-332
[12.]
J.W. Eikelboom, E. Lonn, J. Genest Jr, G. Hankey, S. Yusuf.
Homocyst(e)ine and cardiovascular disease: A critical review of the epidemiologic evidence.
Ann Intern Med, 131 (1999), pp. 363-375
[13.]
H. Refsum, P.M. Ueland, O. Nygard, S.E. Villset.
Homocysteine and cardiovascular disease.
Annu Rev Med, 49 (1998), pp. 31-62
[14.]
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 methilentetrahydrofolate reductase.
Nat Genet, 10 (1995), pp. 111-113
[15.]
A.M. Engbersen, D.G. Franken, G.H. Boers, E.M. Stevens, F.J. Trijbels, H.J. Blom.
Thermolabile 5,10-methylenetatrahydrofolate reductase as a cause of mild hyperhomocysteinemia.
Am J Hum Genet, 56 (1995), pp. 142-150
[16.]
P.F. Jacques, A.G. Bostom, R.R. Williams, R.C. Ellison, J.H. Eckfeldt, I.H. Rosenberg, et al.
Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.
Circulation, 94 (1996), pp. 2322-2323
[17.]
A.B. Guttormsen, P.M. Ueland, I. Nesthus, O. Nygard, J. Schneede, S.E. Vollset, et al.
Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.
J Clin Invest, 98 (1996), pp. 2174-2183
[18.]
J. Selhub, P.F. Jacques, P.W. Wilson, D. Rush, I.H. Rosenberg.
Vitamin status and intake as primary determinants of homocysteinemia in the elderly.
Jama, 270 (1993), pp. 2693-2698
[19.]
J.B. Ubbick, W.J. Vermaak, Van der Merwe, P.J. Becker.
Vitamin B12, Vitamin B6, and Folate nutritional status in men with hypermocysteinemia.
Am J Clin Nutr, 57 (1993), pp. 47-53
[20.]
X. Pinto, M.A. Vilaseca, N. Garcia-Giralt, I. Ferrer, M. Pala, J.F. Meco, et al.
Homocysteine and MTHFR 677C → T allele in Spanish patients with premature coronary artery disease. Case control and famili studies.
Eur J Clin Invest, 3 (2001), pp. 24-30
[21.]
E. Cardo, M.A. Vilaseca, J. Campistol, R. Artuch, C. Colomé, M. Pineda.
Evaluation of hyperhomocysteinemia in children with stroke.
Europ J Paediatr Neurol, 3 (1999), pp. 113-117
[22.]
E. Cardo, E. Monros, C. Colome, R. Artuch, J. Campistol, M. Pineda, et al.
Children with stroke: Polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status.
J Child Neurol, 15 (2000), pp. 295-298
[23.]
M.A. Vilaseca, D. Moyano, I. Ferrer, R. Artuch.
Total-Homocysteine in a pediatric population.
Clin Chem, 43 (1997), pp. 690-692
[24.]
S. Tonstad, H. Refsum, M. Sivertsen, B. Cristophersen, L. Osf, P.M. Ueland.
Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives.
Pediatric Res, 40 (1996), pp. 47-52
[25.]
S. Tonstad, H. Refsum, P.M. Ueland.
Association between plasma total homocysteine and parental history of cardiovascular disease in children with familial hypercholesterolemia.
Circulation, 96 (1997), pp. 1803-1808
[26.]
S. Tonstad, H. Refsum, L. Ose, P.M. Ueland.
The 677C → T mutation in the metilenetetrahydrofolate reductase gene predisposes to hyperhomocysteinemia in children with familial cholesterolemia treated with cholestyramina.
J Pediatr, 132 (1998), pp. 365-368
[27.]
K.J. Greenlund, S.R. Srinivasan, J.H. Xu, E. Dalferes Jr, L. Myers, A. Pickoff, et al.
Plasma homocysteine distribution and its association with parental history of coronary artery disease in black and white children:The Bogalusa Heart Study.
Circulation, 99 (1999), pp. 2144-2149
[28.]
I.M. Graham, L.E. Daly, H.M. Refsum, K. Robinson, L.E. Brattstrom, P.M. Ueland, et al.
Plasma homocysteine as a risk factor for vascular disease: The European concerted action project.
Jama, 277 (1997), pp. 1775-1781
[29.]
O. Fletcher, A.M. Kessling.
MTHFR association with arteriosclerotic vascular diseaseα.
Hum Genet, 103 (1998), pp. 11-21
[30.]
P.M. Ueland, S. Hustad, J. Schneede, H. Refsum, S.E. Vollset.
Biological and clinical implications of the MTHFR C677 → T polymorphism.
Trends Pharmacol Sci, 22 (2001), pp. 195-201
[31.]
L. Soriente, A. Coppola, P. Madonna, A.M. Cerbone, G. Di Minno, G. Orefice, et al.
Homozygous C677 →T mutation of the 5,10-methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in Italian patients with a history of early-onset ischemic stroke.
Stroke, 29 (1998), pp. 869-871
[32.]
L. Brattström, DEL Wilken.
Homocysteine and cardiovascular disease: Cause or effectα.
Am J Clin Nutr, 72 (2000), pp. 315-323
[33.]
H. Morita, J. Taguchi, H. Kurihara, M. Kitaoka, H. Kaneda, Y. Kurihara, et al.
Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease.
Circulation, 95 (1997), pp. 2032-2036
[34.]
T. Ou, K. Yamakawa-Kobayashi, T. Arinami, H. Amemiya, H. Fuji-wara, K. Kawata, et al.
Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: A case-control study.
Atherosclerosis, 137 (1998), pp. 23-28
[35.]
E.E. Delvin, R. Rozen, A. Merouani, J. Genest, M. Lambert.
Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B12 and folate status on plasma homocysteine in children.
Am J Clin Nutr, 72 (2000), pp. 469-473
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