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

Abstract

We investigated the T cell antigen receptor constant (TCR.beta.) .beta.-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 Bg1 II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCR.beta. probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) vs. 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 TCR.beta. heterozygote/DR3+ individuals (odds ratio = 8.31; .chi.2 = 11.82; P = 0.0009); in the absence of TCR.beta. heterozygozity, DR3 was not significantly associated with the disease. These results suggest that TCR.beta. chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals who are HLA DR3 positive.