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
Objective. To determine if a polymorphism in the immunoproteasome subunit L
MP7 was associated with juvenile rheumatoid arthritis (JRA) and had functio
nal significance.
Methods. The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 pa
tients with JRA and 50 controls was determined. JRA subtypes were pauciarti
cular (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 i
nto 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 -DPB1*0201 (p = 0.002 and 0.013). We found no difference in the relati
ve incorporation of LMP7Q and LMP7K into proteasomes.
Conclusions. These results support an association between LMP7QQ homozygosi
ty and JRA, particularly early onset disease. The difference persists with
stratification, at least for DR5(11) and DPB1*0201, suggesting that this ef
fect is unlikely to be due to linkage disequilibrium with HLA alleles known
to be associated with early onset pauciarticular JRA. Importantly, as ther
e does not appear to be functional significance associated with the LMP7 po
lymorphism, this may be a marker for another as yet unidentified susceptibi
lity locus.