Journal of Clinical Endocrinology & Metabolism, Vol 65, 643-646, Copyright © 1987 by Endocrine Society

ARTICLES

Polymorphism of the T cell receptor beta-chain in Graves' disease

A Demaine, KI Welsh, BS Hawe and NR Farid
Department of Molecular Immunogenetics, Guy's Hospital, London, United Kingdom.

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 heterozygosity, 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.

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