Effect of human leukocyte antigen class II genes on acute-onset and slow-onset type 1 diabetes in the Japanese population.

The contribution of the human leukocyte antigen (HLA) subtype to slow-onset type 1 diabetes (T1D), which includes latent autoimmune diabetes in adults (LADA), remains unclear in the Japanese population. We compared the frequencies of HLA DR-DQ haplotypes and genotypes of 72 acute-onset T1D patients, 100 slow-onset T1D patients, and 292 control subjects. The frequencies of DRB10405-DQB10401 (DR4) and DRB11302-DQB10604 (DR13) haplotypes were significantly higher in acute-onset patients, whereas that of the DRB11502-DQB10601 haplotype was significantly lower than those in slow-onset diabetes patients and controls. In contrast, DRB10802-DQB10302 (DR8) and DRB10901-DQB10303 (DR9) haplotypes were significantly more frequent, and the DRB11501-DQB10602 haplotype was extremely rare, in acute-onset patients and slow-onset diabetes patients. Genotype analysis revealed that DR4/9, DR4/13, and DR9/13 in acute-onset patients indicated high odds ratios (6.81, 12.0, and 15.6, respectively), whereas DR4/8 was significantly more frequent in slow-onset diabetes patients, but not in acute-onset patients. Our study demonstrated for the first time that the DR8 haplotype confers susceptibility to slow-onset T1D in the Japanese population. Moreover, there potentially are hierarchies for predisposing haplotypes, namely, DR13 > DR4 > DR9 > DR8 and for protective haplotypes, namely, DRB11501-DQB10602 > DRB11502-DQB10601.