title: Synergy between T cell receptor beta gene polymorphism and HLA-DR4 in susceptibility to rheumatoid arthritis.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rosalind Russell Medical Research Center for Arthritis, University of California at San Francisco, USA.
authors.forename: H
authors.initials: H
authors.lastname: Mu
authors.forename: P
authors.initials: P
authors.lastname: Charmley
authors.forename: M C
authors.initials: MC
authors.lastname: King
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
chemical_list: D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta