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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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