Thyroid Disease (Graves' Disease and Hashimoto's Thyroiditis) in the Japanese Population

Both IDDM and autoimmune thyroid disease (AITD; Graves' disease or Hashimoto's thyroiditis) are believed to develop through a T-cell-mediated autoimmune process, and genetic factors clearly play an important role in this process. To date, studies have shown that the development of IDDM is controlled by multiple susceptibility genes, including HLA class II genes (IDDM1) and a variable number of tandem repeats (VNTR) near the insulin gene (IDDM2) (1). Less is known about AITD susceptibility genes (2). Although several studies have shown that AITD is associated with HLA class II genes, the observed association appeared to be weak. Recently, associations of CTLA-4 gene polymorphisms with both Graves' disease and IDDM have been reported in white populations (3-5). The CTLA-4-linked IDDM susceptibility locus is currently designated IDDM12. CTLA-4 antigen, expressed on activated T-cells, is considered to be important in T-cell regulation (6). In the present study, as a follow-up to our previous studies of HLA class II (DR, DQ) and insulin VNTR genes (7,8), we analyzed CTLA-4 gene polymorphism in Japanese patients with IDDM or AITD. We studied 173 Japanese IDDM patients, 112 Graves' disease patients, and 88 Hashimoto's thyroiditis patients. The diagnosis of IDDM was based on both clinical features and laboratory data, including islet cell antibody (ICA) and the postprandial serum C-peptide value. The diagnosis of AITD was based on clinical findings, thyroid function (thyroid hor-