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Titolo:
Polymorphism in the MHC-encoded LMP7 gene: Association with JRA without functional significance for immunoproteasome assembly
Autore:
Prahalad, S; Kingsbury, DJ; Griffin, TA; Cooper, BL; Glass, DN; Maksymowych, WP; Colbert, RA;
Indirizzi:
Univ Cincinnati, Coll Med, Childrens Hosp,Med Ctr, William S Rowe Div Rheumatol,Dept Pediat, Cincinnati, OH USA Univ Cincinnati Cincinnati OH USA umatol,Dept Pediat, Cincinnati, OH USA Univ Alberta, Dept Med, Edmonton, AB, Canada Univ Alberta Edmonton AB Canada Alberta, Dept Med, Edmonton, AB, Canada
Titolo Testata:
JOURNAL OF RHEUMATOLOGY
fascicolo: 10, volume: 28, anno: 2001,
pagine: 2320 - 2325
SICI:
0315-162X(200110)28:10<2320:PITMLG>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
JUVENILE RHEUMATOID-ARTHRITIS; INTERFERON-GAMMA; ANKYLOSING-SPONDYLITIS; DISEASE SUSCEPTIBILITY; RECOMBINATION HOTSPOT; 20S PROTEASOME; HLA ALLELES; EXPRESSION; SUBUNITS; COMPLEX;
Keywords:
JRA; LMP7; proteasome; association; LMP2; immunoproteasome;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Colbert, RA Childrens Hosp, Med Ctr, Div Rheumatol, 3333 Burnet Ave, Cincinnati, OH 45229 USA Childrens Hosp 3333 Burnet Ave Cincinnati OH USA 45229 229 USA
Citazione:
S. Prahalad et al., "Polymorphism in the MHC-encoded LMP7 gene: Association with JRA without functional significance for immunoproteasome assembly", J RHEUMATOL, 28(10), 2001, pp. 2320-2325

Abstract

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 age6 (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 JRAsubtypes (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 -DPB1*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 withstratification, 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.

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Documento generato il 04/04/20 alle ore 15:19:41