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Human Leukocyte Antigen-A24 and -DQA1¹0301 in Japanese Insulin-Dependent Diabetes Mellitus: Independent Contributions to Susceptibility to the Disease and Additive Contributions to Acceleration of ß-Cell Destruction^,1

Department of Endocrinology and Metabolism, Toranomon Hospital and Okinaka Memorial Institute for Medical Research (K.N., T.K., T.M.), Tokyo 105-8470, Japan; the Department of Molecular Life Science, Tokai University School of Medicine (T.N., H.I.), Isehara 259-1100; and the Hyogo Red Cross Blood Center (Y.N.), Kobe 651-0062, Japan

Address all correspondence and requests for reprints to: Koji Nakanishi, M.D, Department of Endocrinology and Metabolism, Toranomon Hospital, 2–2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.

The aim of this study is to identify insulin-dependent diabetes mellitus (IDDM)-susceptible HLA antigens in IDDM patients who do not have established risk allele, HLA-DQA1*0301, and analyze relationship of these HLA antigens and the degree of ß-cell destruction.

In 139 Japanese IDDM patients and 158 normal controls, HLA-A, -C, -B, -DR and -DQ antigens were typed. Serum C-peptide immunoreactivity response (CPR) to a 100-g oral glucose load 0.033 nmol/l was regarded as complete ß-cell destruction.

All 14 patients without HLA-DQA1*0301 had HLA-A24, whereas only 35 of 58 (60.3%) normal controls without HLA-DQA1*0301 and only 72 of 125 (57.6%) IDDM patients with HLA-DQA1*0301 had this antigen (Pc = 0.0256 and Pc = 0.0080, respectively). CPR in IDDM patients with both HLA-DQA1*0301 and HLA-A24 (0.097 ± 0.163 nmol/L, mean ± SD, n = 65) were lower than in IDDM patients with HLA-DQA1*0301 only (0.219 ± 0.237 nmol/L, n = 45, P < 0.0001) and in IDDM patients with HLA-A24 only (0.187 ± 0.198 nmol/L, n = 14, P = 0.0395).

These results indicate that both HLA-DQA1*0301 and HLA-A24 contribute susceptibility to IDDM independently and accelerate ß-cell destruction in an additive manner.

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