Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional significance for immunoproteasome assembly.

Prahalad, S; Kingsbury, D J; Griffin, T A; Cooper, B L; Glass, D N; Maksymowych, W P; Colbert, R A

Prahalad, S; Kingsbury, D J; Griffin, T A; Cooper, B L; Glass, D N; Maksymowych, W P; Colbert, R A.

Afiliación

Prahalad S; William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45229-3039, USA.

J Rheumatol ; 28(10): 2320-5, 2001 Oct.

Article en En | MEDLINE | ID: mdl-11669176

RESUMEN

OBJECTIVE: To determine if a polymorphism in the immunoproteasome subunit LMP7 was associated with juvenile rheumatoid arthritis (JRA) and had functional significance. METHODS: The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 patients with JRA and 50 controls was determined. JRA subtypes were pauciarticular (53%), polyarticular (33%), and systemic (14%). Onset was before age 6 (early onset) in 60% of patients. The functional significance of the LMP7 polymorphism was determined by comparing incorporation of LMP7Q vs LMP7K into proteasomes. RESULTS: There was an increased frequency of LMP7QQ in patients vs controls (73 vs 56%; p = 0.016), mainly due to the pauciarticular and systemic JRA subtypes (p = 0.037), and more pronounced in early onset disease (77 vs 56%; p = 0.006). The association persisted with stratification for HLA-DR5(11) and -DPB 1 *0201 (p = 0.002 and 0.013). We found no difference in the relative incorporation of LMP7Q and LMP7K into proteasomes. CONCLUSIONS: These results support an association between LMP7QQ homozygosity and JRA, particularly early onset disease. The difference persists with stratification, at least for DR5(11) and DPB1*0201, suggesting that this effect is unlikely to be due to linkage disequilibrium with HLA alleles known to be associated with early onset pauciarticular JRA. Importantly, as there does not appear to be functional significance associated with the LMP7 polymorphism, this may be a marker for another as yet unidentified susceptibility locus.

Asunto(s)

Artritis Juvenil/genética; Artritis Juvenil/inmunología; Cisteína Endopeptidasas/genética; Complejo Mayor de Histocompatibilidad/genética; Complejos Multienzimáticos/genética; Polimorfismo Genético; Proteínas/genética; Niño; Cisteína Endopeptidasas/inmunología; Femenino; Frecuencia de los Genes; Predisposición Genética a la Enfermedad; Genotipo; Antígenos HLA-DR/genética; Antígeno HLA-DR5/genética; Cadenas HLA-DRB1; Humanos; Masculino; Complejos Multienzimáticos/inmunología; Complejo de la Endopetidasa Proteasomal

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Artritis Juvenil / Cisteína Endopeptidasas / Proteínas / Complejo Mayor de Histocompatibilidad / Complejos Multienzimáticos Tipo de estudio: Risk_factors_studies Límite: Child / Female / Humans / Male Idioma: En Revista: J Rheumatol Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Canadá

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links