Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with T cell receptor beta chain gene alleles or haplotypes.
HLA-DR, HLA-DQ, and T cell receptor beta (TCR beta) chain gene polymorphisms were investigated in 43 patients with rheumatoid arthritis (RA), in 10 patients with Felty's syndrome (FS), and in 5 RA multicase families. RA was found to be strongly associated with a DRB1 gene sequence motif present in DR1, DR4-Dw4, and DR4-Dw14 alleles. Ninety-three percent of RA patients were positive for at least 1 of these alleles, providing strong support for the "shared epitope hypothesis." The frequency distribution of this sequence motif suggests a dominant mode of inheritance. All 10 FS patients were DR4-Dw4 positive. Different DR-DQ associations among DR4 positive RA and FS patients indicate heterogeneity in the genetic susceptibility to these 2 disease entities. Furthermore, analyses of TCR V beta 8, V beta 11, and C beta gene polymorphisms did not support the notion of an influence of TCR beta germline allotypes on RA susceptibility.
Center for BioTechnology, Karolinska Institute, Novum, Sweden.
J
J
Wallin
J
J
Hillert
O
O
Olerup
B
B
Carlsson
H
H
Ström
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005258:Felty Syndrome / Q000235:genetics*; D005784:Gene Amplification; D006683:HLA-DQ Antigens / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D006683:HLA-DQ Antigens; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta