Synergy between T cell receptor beta gene polymorphism and HLA-DR4 in susceptibility to rheumatoid arthritis.
OBJECTIVE: To investigate the etiologic significance of germline polymorphisms in the T cell receptor beta variable region 6S7 (TCRBV6S7) gene segment and adjacent loci in susceptibility to rheumatoid arthritis ( RA). METHODS: Ten TCRB allelic polymorphisms were analyzed from 3 groups of white women: 112 with RA, 72 with systemic lupus erythematosus, and 70 healthy controls. All participants were also HLA typed. RESULTS: HLA-DR4+ RA patients showed significantly increased frequencies of TCRBV6S7*1, 13S5P*1 (an allelic variant of BV13S5 promoter), and 12S4*2, compared with healthy controls. The combination of DR4 with either BV6S7*1, 13S5P*1, or 12S4*2 conferred greater risk for RA than HLA-DR4 alone. Pairwise analyses showed a high degree of linkage disequilibrium (P = 10(-5)-10(-8)) between these 3 TCRBV loci that span 47 kilobases (kb). CONCLUSION: Our data suggest that a TCR gene segment in or linked to this 47-kb region may be involved in genetic susceptibility to RA through an interaction with HLA-DR4.[1]References
- Synergy between T cell receptor beta gene polymorphism and HLA-DR4 in susceptibility to rheumatoid arthritis. Mu, H., Charmley, P., King, M.C., Criswell, L.A. Arthritis Rheum. (1996) [Pubmed]
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