Immunogenetics of early-onset insulin-dependent diabetes mellitus among the Japanese: HLA, Gm, BF, GLO, and organ-specific autoantibodies--the J.D.S. study.
The Japan Diabetes Society (JDS) conducted a multicenter study on the immunogenetics of early-onset insulin-dependent diabetes mellitus (IDDM) of the Japanese. Human leukocyte antigen (HLA), properdin factor B (BF), immunoglobulin heavy-chain complex (Gm), and glyoxalase of erythrocytes (GLO) were typed, and organ-specific autoantibodies, including islet cell antibody (ICA), were assayed in 159 Japanese IDDM patients and their family members and in 258 healthy Japanese controls. The HLA-DRw9 phenotype and HLA-Bw61/DRw9 haplotype were significantly increased among the patients with autoantibodies other than ICA but with no autoimmune diseases (RR = 5.84, cP less than 0.001; and RR = 7.45, P less than 0.001), whereas the HLA-DR4 phenotype and HLA-Bw54/DR4 haplotype were significantly increased in those without either the autoantibodies or autoimmune diseases (RR = 2.64, cP less than 0.001; and RR = 4.55, P less than 0.001). The HLA-DR4 phenotype was significantly increased in the patients with autoimmune thyroid diseases (RR = 6.21, cP less than 0.05). In all groups of patients, the HLA-DR2 phenotype was significantly decreased, and the relative risk of the HLA-DRw9/DR4 genotype was highest among all HLA-DR genotypes. No significant association was found between HLA type and the duration or incidence of ICA. Gm types of g and gft were significantly increased in the patients with the autoantibodies (RR = 2.11, P less than 0.05; and RR = 34.11, P less than 0.05), whereas the BF-F phenotype was significantly decreased in the patients either with or without autoantibodies (RR = 0.43, P less than 0.05; and RR = 0.46, P less than 0.05). There was no association between IDDM and GLO type. These data indicate that immunogenetic bases underlying IDDM of the Japanese are heterogeneous, as are those in Caucasians.
Mimura
G
G
Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan.
Kida
K
K
Matsuura
N
N
Toyota
T
T
Kitagawa
T
T
Kobayashi
T
T
Hibi
I
I
Ikeda
Y
Y
Tuchida
I
I
Kuzuya
H
H
D001323:Autoantibodies / Q000032:analysis*; D011415:Complement Factor B / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D004792:Enzyme Precursors / Q000032:analysis*; D004912:Erythrocytes / Q000201:enzymology; D005838:Genotype; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000032:analysis*; D007564:Japan; D007791:Lactoylglutathione Lyase / Q000097:blood*; D008190:Lyases / Q000097:blood*; D008861:Microsomes / Q000276:immunology; D012016:Reference Values; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
D001323:Autoantibodies; D004792:Enzyme Precursors; D006680:HLA Antigens; D007129:Immunoglobulin Gm Allotypes; D013954:Thyroglobulin; D011415:Complement Factor B; D008190:Lyases; D007791:Lactoylglutathione Lyase