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Association of HLA Antigen and Restriction Fragment Length Polymorphism of T Cell Receptor β- Chain Gene with Graves' Disease and Hashimoto's Thyroiditis^*

First Department of Internal Medicine, Nagoya University School of Medicine Nagoya, Japan
Histocompatibility Laboratory Nagoya, Japan
Department of Endocrinology and Metabolism Nagoya, Japan
Nagoya Second Red Cross Hospital, and the Aichi Red Cross Blood Center Nagoya, Japan

Address requests for reprints to: Masafumi Ito, M.D., 1st Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466 Japan.

HLA antigen phenotypes and BglII restriction fragment length polymorphism of T cell receptor β-chain (TCRβ) gene were analyzed in 61 patients with Graves' disease and 50 patients with Hashimoto's thyroiditis. The antigen frequency of HLA-Bw46 in both Graves' disease (23.0%) and Hashimoto's thyroiditis (24.0%) was significantly higher than that in normal population (8.0%), with relative risks (RR) of 3.45 [corrected P (Pc) < 0.009] and 3.66 (Pc < 0.02), respectively. Significantly increased frequency of HLA-B51 antigen was also found in Hashimoto's thyroiditis (40.0% vs. 16.3% in controls; RR, 3.42; Pc < 0.002). Hybridization of BglII-digested DNA with TCRβ probe revealed two alleles of 9.3 and 8.6 kilobases. The allele frequency of 8.6 kilobases in Graves' disease (79%) and Hashimoto's thyroiditis (76%) was significantly higher (P < 0.01 and P < 0.05, respectively) than that in controls (64%). The frequency of homozygous state 8.6/8.6 was significantly increased in both Graves' disease (62%) and Hashimoto's thyroiditis (60%) over that in controls (39%); the RR of 8.6/8.6 in Graves' disease and Hashimoto's thyroiditis were 2.55 (P < 0.01) and 2.31 (P < 0.05), respectively. These results indicate that in Japanese subjects at least two loci are involved in the susceptibility to Graves' disease and Hashimoto's thyroiditis, one related to HLA and another to TCRβ.

^* This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, and Culture and grants from the Ministry of Health and Welfare of Japan.

Received November 23, 1988.

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