Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR)
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
Ángel José González Ordóñeza,**
, Jesús María Medina Rodrígueza, Carmen Rosa Fernández Álvareza, Javier Sánchez Garcíaa, José Manuel Fernández Carreirab, María Victoria Álvarez Martínezc, Eliecer Coto Garcíac
Autor para correspondencia
jagonzalez@medynet.com
Correspondencia: Dr. A.J. González Ordóñez. Servicio de Hematología. Hospital San Agustín. 33400 Avilés. Asturias.
Correspondencia: Dr. A.J. González Ordóñez. Servicio de Hematología. Hospital San Agustín. 33400 Avilés. Asturias.
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Hospital San Agustín. Avilés" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] 1 => array:3 [ "entidad" => "Unidad de Investigación. Hospital San Agustín. Avilés" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff00015" ] 2 => array:3 [ "entidad" => "Laboratorio de Genética Molecular. Hospital Central de Asturias. Oviedo" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff00020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "**" "correspondencia" => "Correspondencia: Dr. A.J. González Ordóñez. Servicio de Hematología. Hospital San Agustín. 33400 Avilés. Asturias." ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "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" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "1999-06-14" "fechaAceptado" => "1999-10-19" "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec220501" "palabras" => array:6 [ 0 => "Polimorfismo ADN" 1 => "Gen MTHFR" 2 => "Metilén tetrahidrofólico reductasa" 3 => "Trombosis venosa" 4 => "Homocisteína" 5 => "Ácido fólico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Fundamento</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Las concentraciones plasmaticas elevadas de homocisteina total (tHcy) se asocian con enfermedad trombotica arterial o venosa. Dependen principalmente del estado nutricional para el acido folico y vitaminas B<span class="elsevierStyleSup">12</span> o B<span class="elsevierStyleSup">6</span> pero tambien de la actividad enzimatica desarrollada por la metilen tetrahidrofolico reductasa (MTHFR). Evaluamos el grado de respuesta de la hiperhomocisteinemia (HHcy) a un sencillo esquema de suplementacion vitaminica respecto al genotipo de MTHFR.</p> <span class="elsevierStyleSectionTitle">Pacientes y metodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se seleccionaron 227 pacientes, diagnosticados de tromboembolia venosa (TEV) y que fueron analizados para tHcy (ayunas) y para el polimorfismo genetico MTHFR-C677T. Cuando la tHcy excedio el limite normal (varones = 16 y mujeres = 15 μmol/l), los pacientes recibieron el equivalente a 1 mg de acido folico, 0,2 mg de vitamina B<span class="elsevierStyleSup">12</span> y 100 mg de vitamina B<span class="elsevierStyleSup">6</span>, diariamente durante 6 sema as. Posteriormente fueron reanalizados y la reduccion fue comparada por genotipos MTHFR, buscando cualquier diferencia en el grado de respuesta.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La tHcy media fue de 12,3 μmol/l (DE = 8). Los 51 pacientes hiperhomocisteinemicos (22%) tenian edad superior (65,1 anos) a los no-HHcy (55,0 anos) (p = 0,0001). La cumplimentacion del tratamiento fue apropiada en 46 pacientes (90%). La tHcy media pretratamiento fue de 23,2 μmol/l (DE = 10,5), y se redujo a 13,0 (DE = 5,9), el 42,1% (p = 0,0001). Por genotipos, los pacientes C/C de 21,0 a 13,2 μmol/l (37%) (n = 18), los C/T de 25,0 a 12,6 μmol/l (46%) (n = 24), y los homozigotos anormales T/T de 22,7 a 14,5 μmol/l (39%) (n = 4), aunque sin evidenciarse diferencias estadisticamente significativas. La respuesta fue completa (normalizandose la tHcy) en el 80% de los casos (37/46). Se observo una correlacion negativa (r = -0.471) (p = 0,005) entre edad y respuesta.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con AF/B<span class="elsevierStyleSup">6</span>/B<span class="elsevierStyleSup">12</span> reduce en forma sencilla, rapida y eficaz (> 40% en 6 semanas) los valores patologicos de tHcy sin ninguna influencia del genotipo MTHFR. Dado que la HHcy parece relacionarse con las recidivas de trombosis venosa, parece prudente determinar la tHcy sistematicamente en pacientes con TEV, para intentar su reduccion en casos seleccionados.</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It esentially depends on the nutritional status of folic acid (FA) and vitamins B<span class="elsevierStyleSup">12</span> or B<span class="elsevierStyleSup">6</span>, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype.</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut off point (men = 16, women = 15 μmol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B<span class="elsevierStyleSup">12</span> and 100 mg of B<span class="elsevierStyleSup">6</span>, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The mean fasting tHcy was 12.3 μmol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) μmol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 μmol/l (37%) (n = 18), the C/T from 25.0 to 12.6 μmol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 μmol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = –0.471) (p = 0.005) was observed between age and response.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The FA/B<span class="elsevierStyleSup">6</span>/B<span class="elsevierStyleSup">12</span> based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Referencias Bibliográficas" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib00005" "etiqueta" => "1." 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 0 | 1 | 1 |
| 2024 Septiembre | 0 | 4 | 4 |
| 2024 Agosto | 0 | 3 | 3 |
| 2024 Julio | 0 | 5 | 5 |
| 2024 Junio | 0 | 1 | 1 |
| 2024 Mayo | 0 | 2 | 2 |
| 2024 Abril | 0 | 5 | 5 |
| 2024 Marzo | 0 | 3 | 3 |
| 2024 Enero | 0 | 1 | 1 |
| 2023 Diciembre | 0 | 3 | 3 |
| 2023 Noviembre | 0 | 7 | 7 |
| 2023 Octubre | 0 | 7 | 7 |
| 2023 Septiembre | 0 | 1 | 1 |
| 2023 Agosto | 0 | 5 | 5 |
| 2023 Julio | 0 | 7 | 7 |
| 2023 Mayo | 0 | 4 | 4 |
| 2023 Marzo | 2 | 2 | 4 |
| 2023 Febrero | 0 | 1 | 1 |
| 2023 Enero | 0 | 3 | 3 |
| 2022 Diciembre | 0 | 1 | 1 |
| 2022 Noviembre | 0 | 5 | 5 |
| 2022 Octubre | 0 | 6 | 6 |
| 2022 Septiembre | 0 | 4 | 4 |
| 2022 Julio | 0 | 4 | 4 |
| 2022 Junio | 0 | 5 | 5 |
| 2022 Mayo | 0 | 5 | 5 |
| 2022 Abril | 0 | 8 | 8 |
| 2022 Marzo | 0 | 3 | 3 |
| 2021 Diciembre | 0 | 1 | 1 |
| 2021 Noviembre | 0 | 5 | 5 |
| 2021 Septiembre | 0 | 1 | 1 |
| 2021 Agosto | 0 | 1 | 1 |
| 2021 Julio | 0 | 2 | 2 |
| 2021 Mayo | 0 | 3 | 3 |
| 2021 Abril | 1 | 0 | 1 |
| 2021 Febrero | 0 | 2 | 2 |
| 2021 Enero | 0 | 2 | 2 |
| 2020 Noviembre | 0 | 2 | 2 |
| 2020 Septiembre | 0 | 1 | 1 |
| 2020 Julio | 0 | 1 | 1 |
| 2020 Junio | 0 | 4 | 4 |
| 2020 Mayo | 0 | 12 | 12 |
| 2020 Abril | 0 | 2 | 2 |
| 2020 Marzo | 0 | 4 | 4 |
| 2020 Enero | 0 | 8 | 8 |
| 2019 Diciembre | 0 | 7 | 7 |
| 2019 Noviembre | 0 | 1 | 1 |
| 2019 Octubre | 0 | 5 | 5 |
| 2019 Septiembre | 0 | 3 | 3 |
| 2019 Agosto | 1 | 3 | 4 |
| 2019 Julio | 0 | 9 | 9 |
| 2019 Junio | 0 | 6 | 6 |
| 2019 Mayo | 0 | 23 | 23 |
| 2018 Septiembre | 0 | 1 | 1 |
| 2018 Enero | 0 | 1 | 1 |
| 2017 Octubre | 1 | 1 | 2 |
| 2017 Septiembre | 9 | 11 | 20 |
| 2017 Agosto | 9 | 1 | 10 |
| 2017 Julio | 12 | 2 | 14 |
| 2017 Junio | 11 | 7 | 18 |
| 2017 Mayo | 22 | 7 | 29 |
| 2017 Abril | 16 | 1 | 17 |
| 2017 Marzo | 23 | 39 | 62 |
| 2017 Febrero | 10 | 7 | 17 |
| 2017 Enero | 5 | 0 | 5 |
| 2016 Diciembre | 41 | 3 | 44 |
| 2016 Noviembre | 35 | 5 | 40 |
| 2016 Octubre | 43 | 3 | 46 |
| 2016 Septiembre | 31 | 5 | 36 |
| 2016 Agosto | 18 | 1 | 19 |
| 2016 Julio | 24 | 1 | 25 |
| 2016 Junio | 26 | 0 | 26 |
| 2016 Mayo | 22 | 3 | 25 |
| 2016 Abril | 17 | 0 | 17 |
| 2016 Marzo | 16 | 1 | 17 |
| 2016 Febrero | 19 | 1 | 20 |
| 2016 Enero | 15 | 0 | 15 |
| 2015 Diciembre | 22 | 0 | 22 |
| 2015 Noviembre | 30 | 0 | 30 |
| 2015 Octubre | 34 | 0 | 34 |
| 2015 Septiembre | 30 | 0 | 30 |
| 2015 Agosto | 27 | 0 | 27 |
| 2015 Julio | 14 | 0 | 14 |
| 2015 Junio | 6 | 0 | 6 |
| 2015 Mayo | 19 | 0 | 19 |
| 2015 Abril | 12 | 0 | 12 |
| 2015 Marzo | 22 | 0 | 22 |
| 2015 Febrero | 23 | 0 | 23 |
| 2015 Enero | 16 | 0 | 16 |
| 2014 Diciembre | 19 | 0 | 19 |
| 2014 Noviembre | 3 | 0 | 3 |
| 2014 Octubre | 7 | 0 | 7 |
| 2014 Septiembre | 12 | 0 | 12 |
| 2014 Agosto | 3 | 0 | 3 |
| 2014 Julio | 7 | 0 | 7 |
| 2014 Junio | 6 | 0 | 6 |
| 2014 Mayo | 3 | 0 | 3 |
| 2014 Abril | 2 | 0 | 2 |
| 2014 Marzo | 2 | 0 | 2 |
| 2014 Febrero | 3 | 0 | 3 |
| 2014 Enero | 7 | 0 | 7 |
| 2013 Diciembre | 7 | 0 | 7 |
| 2013 Noviembre | 9 | 0 | 9 |
| 2013 Octubre | 14 | 0 | 14 |
| 2013 Septiembre | 7 | 0 | 7 |
| 2013 Agosto | 9 | 0 | 9 |
| 2013 Mayo | 1 | 0 | 1 |
| 2000 Enero | 983 | 0 | 983 |
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