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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La enfermedad cel&#237;aca est&#225; estrechamente relacionada con ciertos ant&#237;genos HLA&#46; El objetivo de este estudio es valorar el desequilibrio de <span class="elsevierStyleItalic">linkage</span> existente entre los diferentes ant&#237;genos y las frecuencias de los haplotipos de dos loci&#58; <span class="elsevierStyleItalic">HLA A&#47;B&#44; A&#47;C&#44; A&#47;DR&#44; A&#47;DQ&#59; HLA B&#47;C&#44; B&#47;DR&#44; B&#47;DQ&#59; HLA C&#47;DR&#44; C&#47;DQ y HLA DR&#47;DQ</span>&#44; en ni&#241;os con enfermedad cel&#237;aca y en poblaci&#243;n control de la misma zona geogr&#225;fica&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</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 ni&#241;os cel&#237;acos&#44; de edades comprendidas al diagn&#243;stico entre 5 meses y 18 a&#241;os y en la poblaci&#243;n control de la misma regi&#243;n geogr&#225;fica &#40;Arag&#243;n&#44; regi&#243;n del noreste de Espa&#241;a&#41;&#46; Para su estudio se ha utilizado la t&#233;cnica de microlinfocitotoxicidad&#46; La frecuencia de cada haplotipo de dos loci &#40;Hij&#41; depende de la frecuencia g&#233;nica de cada alelo &#40;pi y pj&#41; y de un factor de correcci&#243;n &#916;&#44; seg&#250;n la f&#243;rmula&#58; H<span class="elsevierStyleInf">ij</span> &#61; &#916;<span class="elsevierStyleInf">ij</span>&#43;&#40;p<span class="elsevierStyleInf">i</span> &#215; p<span class="elsevierStyleInf">j</span>&#41;&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La estimaci&#243;n de la asociaci&#243;n entre gametos se ha determinado mediante tablas de contingencia 2 &#215; 2&#44; realizadas independientemente para cada una de las combinaciones fenot&#237;picas entre especificidades de dos loci diferentes&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En los enfermos cel&#237;acos&#44; los haplotipos m&#225;s frecuentes y significativos son&#58; <span class="elsevierStyleItalic">A1&#47;B8&#44; A9&#47;B5&#44; A19&#47;B12&#44; A28&#47;B22&#44; A28&#47;Cw1&#44; A9&#47;DQ3&#44; B8&#47;Cw7&#44; B18&#47;Cw5&#44; B22&#47;Cw1&#44; B5&#47;DR5&#44; B8&#47;DR3&#44; B12&#47;DR7&#44; B5&#47;DQ3&#44; DR3&#47;DQ2&#44; DR4&#47;DQ8 &#40;3&#41; y DR5&#47;DQ3</span>&#46; Entre los haplotipos A&#47;DR no se ha encontrado ninguno significativo&#46; Los haplotipos <span class="elsevierStyleItalic">B18&#47;Cw7&#44; B12&#47;DR3&#44; Cw4&#47;DR3 y DR3&#47;DQ3</span> tienen un desequilibrio de linkage negativo estad&#237;sticamente significativo&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Del estudio comparativo entre ni&#241;os cel&#237;acos y poblaci&#243;n se concluye que las asociaciones de los haplotipos <span class="elsevierStyleItalic">A1&#47;B8&#44; A19&#47;B12&#44; B8&#47;DR3&#44; B12&#47;DR7 y DR3&#47;DQ2</span> son significativamente m&#225;s frecuentes en los cel&#237;acos que en la poblaci&#243;n control y su presencia puede predisponer al padecimiento de dicha enfermedad&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Celiac disease is closely correlated with certain human lymphocyte antigen &#40;HLA&#41; alleles&#46; The aim of this study was to compare linkage disequilibrium parameters and the frequencies of the two loci haplotypes&#58; <span class="elsevierStyleItalic">HLA A&#47;B&#44; A&#47;C&#44; A&#47;DR&#44; A&#47;DQ&#59; HLA B&#47;C&#44; B&#47;DR&#44; B&#47;DQ&#59; HLA C&#47;DR&#44; C&#47;DQ</span> and <span class="elsevierStyleItalic">HLA DR&#47;DQ</span> in children with celiac disease and in a control population within the same geographical area&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Thirty-eight children with celiac disease&#44; aged 5 months to 18 years at diagnosis&#44; were HLA typed by microlymphocytotoxicity assay using T-and B-cells separated by monoclonal antibody-labeled immunomagnetic particles&#46; The frequency of each haplotype of two loci &#40;Hij&#41; depends on the frequency of each allele &#40;pi and pj&#41; and on a correction factor delta&#44; according to the formula&#58; H<span class="elsevierStyleInf">ij</span> &#61; &#916;<span class="elsevierStyleInf">ij</span>&#43;&#40;p<span class="elsevierStyleInf">i</span> &#215; p<span class="elsevierStyleInf">j</span>&#41;&#46; The existence of a correction factor delta&#44; or linkage disequilibrium&#44; was assessed by a chi-square test using 2 &#215; 2 contingency tables for gametic association&#46;</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&#47;B8&#44; A9&#47;B5&#44; A19&#47;B12&#44; A28&#47;B22&#44; A28&#47;Cw1&#44; A9&#47;DQ3&#44; B8&#47;Cw7&#44; B18&#47;Cw5&#44; B22&#47;Cw1&#44; B5&#47;DR5&#44; B8&#47;DR3&#44; B12&#47;DR7&#44; B5&#47;DQ3&#44; DR3&#47;DQ2&#44; DR4&#47;DQ8 &#40;3&#41; and DR5&#47;DQ3</span>&#44; showing a positive linkage disequilibrium&#46; Negative linkage disequilibrium was found between <span class="elsevierStyleItalic">B18&#47;Cw7&#44; B12&#47;DR3&#44; Cw4&#47;DR3</span> and <span class="elsevierStyleItalic">DR3&#47;DQ3</span>&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Our findings show that the frequency of <span class="elsevierStyleItalic">A1&#47;B8&#44; A19&#47;B12&#44; B8&#47;DR3&#44; B12&#47;DR7</span> and <span class="elsevierStyleItalic">DR3&#47;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&#46;</p>"
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Vol. 54. Núm. 1.
Páginas 7-12 (enero 2001)
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Vol. 54. Núm. 1.
Páginas 7-12 (enero 2001)
Acceso a texto completo
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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M.aY. Ruiz del Pradoa,
Autor para correspondencia
med024347@nacom.es

Correspondencia: Jorge Vigón, 42, 4.° dcha. 26003 Logroño
, J.L. Olivares Lópeza, A. Lázaro Almarzaa, M.aP. Lasierra Díazb
a Departamento de Pediatría. Hospital Clínico Universitario Lozano Blesa. Zaragoza
b Departamento de Microbiología. Hospital Clínico Universitario Lozano Blesa. Zaragoza
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Objetivo

La enfermedad celíaca está estrechamente relacionada con ciertos antígenos HLA. El objetivo de este estudio es valorar el desequilibrio de linkage existente entre los diferentes antígenos y las frecuencias de los haplotipos de dos loci: 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, en niños con enfermedad celíaca y en población control de la misma zona geográfica.

Pacientes y métodos

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: Hij = Δij+(pi × pj).

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.

Resultados

En los enfermos celíacos, los haplotipos más frecuentes y significativos son: 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. Entre los haplotipos A/DR no se ha encontrado ninguno significativo. Los haplotipos B18/Cw7, B12/DR3, Cw4/DR3 y DR3/DQ3 tienen un desequilibrio de linkage negativo estadísticamente significativo.

Conclusiones

Del estudio comparativo entre niños celíacos y población se concluye que las asociaciones de los haplotipos A1/B8, A19/B12, B8/DR3, B12/DR7 y DR3/DQ2 son significativamente más frecuentes en los celíacos que en la población control y su presencia puede predisponer al padecimiento de dicha enfermedad.

Palabras clave:
Enfermedad celíaca
Sistema HLA
Desequilibrio de linkage
Frecuencia haplotípica
Objective

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: HLA A/B, A/C, A/DR, A/DQ; HLA B/C, B/DR, B/DQ; HLA C/DR, C/DQ and HLA DR/DQ in children with celiac disease and in a control population within the same geographical area.

Methods

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: Hij = Δij+(pi × pj). 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.

Results

Among children with celiac disease the most frequent and significant haplotypes were 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, showing a positive linkage disequilibrium. Negative linkage disequilibrium was found between B18/Cw7, B12/DR3, Cw4/DR3 and DR3/DQ3.

Conclusions

Our findings show that the frequency of A1/B8, A19/B12, B8/DR3, B12/DR7 and DR3/DQ2 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.

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