Haplotipos HLA de dos loci en niños celíacos. Desequilibrio de linkage y frecuencias haplotípicas. Estudio comparativo con una población control
Two loci hla haplotypes in celiac children and healthy subjects. estimate of linkage disequilibrium parameters and haplotype frequencies
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Ruibal Francisco, O. Pérez Rodríguez, M.J. Dorado Moles, E. Piñero Martínez, M.<span class="elsevierStyleSup">a</span>L. Jiménez Alamo, G. Bueno Lozano" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Ruibal Francisco" ] 1 => array:2 [ "nombre" => "O." "apellidos" => "Pérez Rodríguez" ] 2 => array:2 [ "nombre" => "M.J." "apellidos" => "Dorado Moles" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "Piñero Martínez" ] 4 => array:2 [ "nombre" => "M.<span class="elsevierStyleSup">a</span>L." "apellidos" => "Jiménez Alamo" ] 5 => array:2 [ "nombre" => "G." "apellidos" => "Bueno Lozano" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403301786432?idApp=UINPBA00005H" "url" => "/16954033/0000005400000001/v1_201307051535/S1695403301786432/v1_201307051535/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1695403301786419" "issn" => "16954033" "doi" => "10.1016/S1695-4033(01)78641-9" "estado" => "S300" "fechaPublicacion" => "2001-01-01" "aid" => "78641" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 0 "subdocumento" => "edi" "cita" => "An Pediatr (Barc). 2001;54:4-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2949 "formatos" => array:3 [ "EPUB" => 49 "HTML" => 2406 "PDF" => 494 ] ] "es" => array:7 [ "idiomaDefecto" => true "titulo" => "Síndrome de apneas-hipopneas durante el sueño en el niño" "tienePdf" => "es" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "4" "paginaFinal" => "6" ] ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Durán Cantolla, R. Rubio Aramendi" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Durán Cantolla" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Rubio Aramendi" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403301786419?idApp=UINPBA00005H" "url" => "/16954033/0000005400000001/v1_201307051535/S1695403301786419/v1_201307051535/es/main.assets" ] "es" => array:14 [ "idiomaDefecto" => true "titulo" => "Haplotipos HLA de dos loci en niños celíacos. Desequilibrio de <span class="elsevierStyleItalic">linkage</span> y frecuencias haplotípicas. Estudio comparativo con una población control" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "7" "paginaFinal" => "12" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.<span class="elsevierStyleSup">a</span>Y. Ruiz del Prado, J.L. Olivares López, A. Lázaro Almarza, M.<span class="elsevierStyleSup">a</span>P. Lasierra Díaz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.<span class="elsevierStyleSup">a</span>Y." "apellidos" => "Ruiz del Prado" "email" => array:1 [ 0 => "med024347@nacom.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.L." "apellidos" => "Olivares López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Lázaro Almarza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.<span class="elsevierStyleSup">a</span>P." "apellidos" => "Lasierra Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Pediatría. Hospital Clínico Universitario Lozano Blesa. Zaragoza" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Microbiología. Hospital Clínico Universitario Lozano Blesa. Zaragoza" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondencia: Jorge Vigón, 42, 4.° dcha. 26003 Logroño" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Two loci hla haplotypes in celiac children and healthy subjects. estimate of linkage disequilibrium parameters and haplotype frequencies" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2000-07-31" "fechaAceptado" => "2000-08-31" "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec186550" "palabras" => array:4 [ 0 => "Enfermedad celíaca" 1 => "Sistema HLA" 2 => "Desequilibrio de linkage" 3 => "Frecuencia haplotípica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La enfermedad celíaca está estrechamente relacionada con ciertos antígenos HLA. El objetivo de este estudio es valorar el desequilibrio de <span class="elsevierStyleItalic">linkage</span> existente entre los diferentes antígenos y las frecuencias de los haplotipos de dos loci: <span class="elsevierStyleItalic">HLA A/B, A/C, A/DR, A/DQ; HLA B/C, B/DR, B/DQ; HLA C/DR, C/DQ y HLA DR/DQ</span>, en niños con enfermedad celíaca y en población control de la misma zona geográfica.</p> <span class="elsevierStyleSectionTitle">Pacientes y métodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se han determinado y comparado el valor del desequilibrio de linkage y frecuencias de los haplotipos de dos loci en 38 niños celíacos, de edades comprendidas al diagnóstico entre 5 meses y 18 años y en la población control de la misma región geográfica (Aragón, región del noreste de España). Para su estudio se ha utilizado la técnica de microlinfocitotoxicidad. La frecuencia de cada haplotipo de dos loci (Hij) depende de la frecuencia génica de cada alelo (pi y pj) y de un factor de corrección Δ, según la fórmula: H<span class="elsevierStyleInf">ij</span> = Δ<span class="elsevierStyleInf">ij</span>+(p<span class="elsevierStyleInf">i</span> × p<span class="elsevierStyleInf">j</span>).</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La estimación de la asociación entre gametos se ha determinado mediante tablas de contingencia 2 × 2, realizadas independientemente para cada una de las combinaciones fenotípicas entre especificidades de dos loci diferentes.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En los enfermos celíacos, los haplotipos más frecuentes y significativos son: <span class="elsevierStyleItalic">A1/B8, A9/B5, A19/B12, A28/B22, A28/Cw1, A9/DQ3, B8/Cw7, B18/Cw5, B22/Cw1, B5/DR5, B8/DR3, B12/DR7, B5/DQ3, DR3/DQ2, DR4/DQ8 (3) y DR5/DQ3</span>. Entre los haplotipos A/DR no se ha encontrado ninguno significativo. Los haplotipos <span class="elsevierStyleItalic">B18/Cw7, B12/DR3, Cw4/DR3 y DR3/DQ3</span> tienen un desequilibrio de linkage negativo estadísticamente significativo.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Del estudio comparativo entre niños celíacos y población se concluye que las asociaciones de los haplotipos <span class="elsevierStyleItalic">A1/B8, A19/B12, B8/DR3, B12/DR7 y DR3/DQ2</span> son significativamente más frecuentes en los celíacos que en la población control y su presencia puede predisponer al padecimiento de dicha enfermedad.</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Celiac disease is closely correlated with certain human lymphocyte antigen (HLA) alleles. The aim of this study was to compare linkage disequilibrium parameters and the frequencies of the two loci haplotypes: <span class="elsevierStyleItalic">HLA A/B, A/C, A/DR, A/DQ; HLA B/C, B/DR, B/DQ; HLA C/DR, C/DQ</span> and <span class="elsevierStyleItalic">HLA DR/DQ</span> in children with celiac disease and in a control population within the same geographical area.</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Thirty-eight children with celiac disease, aged 5 months to 18 years at diagnosis, were HLA typed by microlymphocytotoxicity assay using T-and B-cells separated by monoclonal antibody-labeled immunomagnetic particles. The frequency of each haplotype of two loci (Hij) depends on the frequency of each allele (pi and pj) and on a correction factor delta, according to the formula: H<span class="elsevierStyleInf">ij</span> = Δ<span class="elsevierStyleInf">ij</span>+(p<span class="elsevierStyleInf">i</span> × p<span class="elsevierStyleInf">j</span>). The existence of a correction factor delta, or linkage disequilibrium, was assessed by a chi-square test using 2 × 2 contingency tables for gametic association.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Among children with celiac disease the most frequent and significant haplotypes were <span class="elsevierStyleItalic">A1/B8, A9/B5, A19/B12, A28/B22, A28/Cw1, A9/DQ3, B8/Cw7, B18/Cw5, B22/Cw1, B5/DR5, B8/DR3, B12/DR7, B5/DQ3, DR3/DQ2, DR4/DQ8 (3) and DR5/DQ3</span>, showing a positive linkage disequilibrium. Negative linkage disequilibrium was found between <span class="elsevierStyleItalic">B18/Cw7, B12/DR3, Cw4/DR3</span> and <span class="elsevierStyleItalic">DR3/DQ3</span>.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Our findings show that the frequency of <span class="elsevierStyleItalic">A1/B8, A19/B12, B8/DR3, B12/DR7</span> and <span class="elsevierStyleItalic">DR3/DQ2</span> haplotypes is higher in children with celiac disease than in the control population and suggest that these two loci haplotypes confer susceptibility to celiac disease.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:41 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 6 | 10 | 16 |
| 2024 Octubre | 53 | 64 | 117 |
| 2024 Septiembre | 61 | 62 | 123 |
| 2024 Agosto | 69 | 102 | 171 |
| 2024 Julio | 48 | 44 | 92 |
| 2024 Junio | 76 | 41 | 117 |
| 2024 Mayo | 50 | 33 | 83 |
| 2024 Abril | 54 | 37 | 91 |
| 2024 Marzo | 65 | 53 | 118 |
| 2024 Febrero | 63 | 41 | 104 |
| 2024 Enero | 89 | 36 | 125 |
| 2023 Diciembre | 81 | 24 | 105 |
| 2023 Noviembre | 60 | 48 | 108 |
| 2023 Octubre | 52 | 31 | 83 |
| 2023 Septiembre | 32 | 23 | 55 |
| 2023 Agosto | 35 | 17 | 52 |
| 2023 Julio | 39 | 27 | 66 |
| 2023 Junio | 42 | 27 | 69 |
| 2023 Mayo | 53 | 20 | 73 |
| 2023 Abril | 39 | 16 | 55 |
| 2023 Marzo | 47 | 32 | 79 |
| 2023 Febrero | 29 | 14 | 43 |
| 2023 Enero | 40 | 33 | 73 |
| 2022 Diciembre | 47 | 25 | 72 |
| 2022 Noviembre | 63 | 34 | 97 |
| 2022 Octubre | 51 | 35 | 86 |
| 2022 Septiembre | 45 | 27 | 72 |
| 2022 Agosto | 66 | 46 | 112 |
| 2022 Julio | 37 | 43 | 80 |
| 2022 Junio | 35 | 38 | 73 |
| 2022 Mayo | 30 | 36 | 66 |
| 2022 Abril | 36 | 50 | 86 |
| 2022 Marzo | 30 | 43 | 73 |
| 2022 Febrero | 33 | 27 | 60 |
| 2022 Enero | 35 | 43 | 78 |
| 2021 Diciembre | 26 | 40 | 66 |
| 2021 Noviembre | 38 | 37 | 75 |
| 2021 Octubre | 54 | 47 | 101 |
| 2021 Septiembre | 26 | 41 | 67 |
| 2021 Agosto | 38 | 30 | 68 |
| 2021 Julio | 42 | 35 | 77 |
| 2021 Junio | 35 | 51 | 86 |
| 2021 Mayo | 26 | 32 | 58 |
| 2021 Abril | 42 | 69 | 111 |
| 2021 Marzo | 90 | 33 | 123 |
| 2021 Febrero | 58 | 24 | 82 |
| 2021 Enero | 36 | 16 | 52 |
| 2020 Diciembre | 27 | 11 | 38 |
| 2020 Noviembre | 30 | 16 | 46 |
| 2020 Octubre | 22 | 17 | 39 |
| 2020 Septiembre | 36 | 10 | 46 |
| 2020 Agosto | 18 | 12 | 30 |
| 2020 Julio | 26 | 8 | 34 |
| 2020 Junio | 34 | 11 | 45 |
| 2020 Mayo | 38 | 22 | 60 |
| 2020 Abril | 48 | 18 | 66 |
| 2020 Marzo | 21 | 9 | 30 |
| 2020 Febrero | 27 | 18 | 45 |
| 2020 Enero | 43 | 19 | 62 |
| 2019 Diciembre | 34 | 19 | 53 |
| 2019 Noviembre | 19 | 6 | 25 |
| 2019 Octubre | 25 | 7 | 32 |
| 2019 Septiembre | 18 | 20 | 38 |
| 2019 Agosto | 23 | 18 | 41 |
| 2019 Julio | 23 | 26 | 49 |
| 2019 Junio | 25 | 45 | 70 |
| 2019 Mayo | 35 | 25 | 60 |
| 2019 Abril | 24 | 20 | 44 |
| 2019 Marzo | 18 | 12 | 30 |
| 2019 Febrero | 22 | 6 | 28 |
| 2019 Enero | 22 | 12 | 34 |
| 2018 Diciembre | 19 | 11 | 30 |
| 2018 Noviembre | 20 | 15 | 35 |
| 2018 Octubre | 33 | 15 | 48 |
| 2018 Septiembre | 12 | 7 | 19 |
| 2018 Agosto | 2 | 0 | 2 |
| 2018 Mayo | 2 | 0 | 2 |
| 2018 Abril | 10 | 0 | 10 |
| 2018 Marzo | 7 | 0 | 7 |
| 2018 Febrero | 7 | 0 | 7 |
| 2018 Enero | 8 | 0 | 8 |
| 2017 Diciembre | 5 | 0 | 5 |
| 2017 Noviembre | 12 | 0 | 12 |
| 2017 Octubre | 17 | 0 | 17 |
| 2017 Septiembre | 7 | 0 | 7 |
| 2017 Agosto | 4 | 0 | 4 |
| 2017 Julio | 23 | 1 | 24 |
| 2017 Junio | 14 | 6 | 20 |
| 2017 Mayo | 23 | 9 | 32 |
| 2017 Abril | 9 | 8 | 17 |
| 2017 Marzo | 9 | 14 | 23 |
| 2017 Febrero | 12 | 6 | 18 |
| 2017 Enero | 5 | 2 | 7 |
| 2016 Diciembre | 31 | 7 | 38 |
| 2016 Noviembre | 27 | 10 | 37 |
| 2016 Octubre | 28 | 11 | 39 |
| 2016 Septiembre | 41 | 10 | 51 |
| 2016 Agosto | 39 | 15 | 54 |
| 2016 Julio | 14 | 12 | 26 |
| 2016 Junio | 1 | 0 | 1 |
| 2016 Abril | 1 | 0 | 1 |
| 2016 Marzo | 4 | 12 | 16 |
| 2016 Febrero | 1 | 0 | 1 |
| 2016 Enero | 3 | 0 | 3 |
| 2015 Diciembre | 2 | 0 | 2 |
| 2015 Septiembre | 1 | 0 | 1 |
| 2015 Agosto | 1 | 0 | 1 |
| 2015 Julio | 28 | 27 | 55 |
| 2015 Junio | 13 | 0 | 13 |
| 2015 Mayo | 24 | 9 | 33 |
| 2015 Abril | 21 | 10 | 31 |
| 2015 Marzo | 25 | 8 | 33 |
| 2015 Febrero | 9 | 9 | 18 |
| 2015 Enero | 21 | 1 | 22 |
| 2014 Diciembre | 34 | 3 | 37 |
| 2014 Noviembre | 12 | 0 | 12 |
| 2014 Octubre | 19 | 2 | 21 |
| 2014 Septiembre | 17 | 5 | 22 |
| 2014 Agosto | 16 | 4 | 20 |
| 2014 Julio | 18 | 4 | 22 |
| 2014 Junio | 29 | 3 | 32 |
| 2014 Mayo | 33 | 4 | 37 |
| 2014 Abril | 25 | 3 | 28 |
| 2014 Marzo | 24 | 12 | 36 |
| 2014 Febrero | 17 | 8 | 25 |
| 2014 Enero | 18 | 7 | 25 |
| 2013 Diciembre | 26 | 18 | 44 |
| 2013 Noviembre | 13 | 7 | 20 |
| 2013 Octubre | 20 | 13 | 33 |
| 2013 Septiembre | 18 | 11 | 29 |
| 2013 Agosto | 22 | 16 | 38 |
| 2013 Julio | 10 | 4 | 14 |
| 2013 Junio | 6 | 7 | 13 |
| 2013 Mayo | 5 | 2 | 7 |
| 2013 Abril | 13 | 2 | 15 |
| 2013 Marzo | 13 | 3 | 16 |
| 2013 Febrero | 32 | 5 | 37 |
| 2013 Enero | 39 | 1 | 40 |
| 2012 Diciembre | 50 | 3 | 53 |
| 2012 Noviembre | 37 | 3 | 40 |
| 2012 Octubre | 16 | 0 | 16 |
| 2012 Septiembre | 4 | 1 | 5 |
| 2001 Enero | 2164 | 0 | 2164 |
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