Open Access Open Badges Research article

Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case–control study

Hulya Bukulmez1234*, Mark Fife5, Monica Tsoras1, Susan D Thompson1, Natalie A Twine5, Patricia Woo5, Jane M Olson2, Robert C Elston2, David N Glass1 and Robert A Colbert1

Author Affiliations

1 William S. Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA

2 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA

3 Department of Genetics, Case Western Reserve University, Cleveland, Ohio, USA

4 Pediatric Rheumatology, Pediatrics, Metro Health Medical Center, Case Western Reserve University, Cleveland, Ohio, USA

5 The Center for Pediatric and Adolescent Rheumatology, University College London, London, UK

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Arthritis Res Ther 2005, 7:R285-R290  doi:10.1186/ar1480

Published: 11 January 2005


Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case–control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (χ2 = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6.

association; linkage; juvenile rheumatoid arthritis; tapasin; TPSN; transmission disequilibrium testing