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 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.
Subject(s)
Arthritis, Juvenile/genetics , Arthritis, Juvenile/immunology , Cysteine Endopeptidases/genetics , Major Histocompatibility Complex/genetics , Multienzyme Complexes/genetics , Polymorphism, Genetic , Proteins/genetics , Child , Cysteine Endopeptidases/immunology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , HLA-DR Antigens/genetics , HLA-DR5 Antigen/genetics , HLA-DRB1 Chains , Humans , Male , Multienzyme Complexes/immunology , Proteasome Endopeptidase ComplexABSTRACT
Senior Adult Educational Programs are being implemented widely as an avenue to social reorientation and greater fulfillment after retirement. Although this investigation of one program reveals limited impact on the SMSA, the findings do indicate successful retirement adjustment for program participants. The average enrollee is white, middle-class, Protestant and female, and living in close proximity to the Community College campus where the program is based. The data indicate that participation in the Senior Adult Education Program eases the transition from the primary occupational role into the retirement role. Intergenerational social distance appears to be minimal between older and younger college students, thus facilitating the sharing of a common campus.
