Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor.
Cornélis F., Hardwick L., Flipo RM., Martinez M., Lasbleiz S., Prud'homme JF., Tran TH., Walsh S., Delaye A., Nicod A., Loste MN., Lepage V., Gibson K., Pile K., Djoulah S., Danzé PM., Lioté F., Charron D., Weissenbach J., Kuntz D., Bardin T., Wordsworth BP.
OBJECTIVE: To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). CONCLUSION: These findings show evidence that TCRA is an RA susceptibility locus.