OBJECTIVES--To investigate whether T-cell receptor (TCR) beta chain germline alleles, either alone or in combination with a particular HLA-genotype, are associated with rheumatoid arthritis (RA). METHODS--Three restriction fragment length polymorphisms (RFLPs), detected with TCR constant (TCRBC2) and variable (TCRBV8, TCRBV11) gene segments were analysed in a representative group of Belgian, HLA class II-typed patients with RA, and in a group of Belgian control subjects. RESULTS--The study confirmed the known association of RA with the HLA-DRB1*0401/0404 genotype (RR = 2.14, 95% CI = 1.16-4.00) in the Belgian RA population. This association was even more pronounced in the patients with more severe RA (RR = 3.26, 95% CI = 1.55-6.89). These data suggest that the HLA-DRB1*04 genotype can be used as a marker for disease severity. Similar frequencies in patients and controls were observed for all TCRB RFLPs studied, and this was in spite of subgrouping the RA population according to criteria for disease stratification. CONCLUSION--While a clear association with HLA DRB1*0401/0404 is observed, no interactive effects were seen with RA, DR4, TCRBC2 and TCRBV alleles, implying that the combined presence of these polymorphic markers does not cause an increased susceptibility to RA, and does not predispose for more aggressive RA, nor for familial aggregation of the disease. These results argue against the hypothesis that TCRB polymorphisms play a crucial role in the susceptibility for RA.
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