(JDDM12 Locus) With Acute-Onset and Insulin-Depleted IDDM as Well as Autoimmune 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-medi-ated autoimmune process, and genetic factors clearly play an important role in this process. To date, stud-ies 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, asso-ciations 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 cur-rently designated IDDM12. CTLA-4 antigen, expressed on activated T-cells, is considered to be important in T-cell reg-ulation (6). In the present study, as a follow-up to our previ