Polymorphism of the T Cell Receptor β-Chain in Graves' Disease*

We investigated the T cell antigen receptor constant (TCRβ) β-chain genes of patients with Graves' disease using restriction fragment length polymorphism analysis. Genomic DNA from patients and normal subjects was digested with the restriction endonuclease Bgl II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCRβ probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) us. 42.1% in normal subjects (P = 0.003). Using the complex phenotype TCR homozygote (hetero) DR3 as a reference (odds ratio = 1.00), we found that the risk for Graves' disease was restricted to TCRβ heterozygote/DR3+ individuals (odds ratio = 8.31; χ2 = 11.82; P = 0.0009); in the absence of TCRβ heterozygozity, DR3 was not significantly associated with the disease. These results suggest that TCRβ chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals...