抄録
Objective: Type 1 diabetes (T1D) is an organ-specific autoimmune disease triggered by both genetic and environmental
factors. Adult-onset T1D in Japan is frequently associated with autoimmune thyroid disease (AITD), and more than half of the
T1D cases are preceded by AITD. We investigated whether the human leukocyte antigen (HLA) class II (DR/DQ) gene, the
major genetic risk factor for T1D, is useful in identifying individuals at high risk of developing T1D among Japanese AITD patients.
Design/Patients: We genotyped the HLA class II (DR/DQ) gene in 82 patients with AITD complicated with T1D (AITD+T1D),
131 AITD patients without T1D (AITDw/oT1D), and 222 healthy subjects as controls.
Results: Compared to the controls, the AITD+T1D group had a significantly higher rate of the T1D-susceptible haplotype
DRB1*0405-DQB1*0401, but the AITDw/oT1D group did not. Compared to the controls, the T1D-protective haplotypes
DRB1*1501-DQB1*0602/DRB1*1502-DQB1*0601 were significantly less frequent in the AITD+T1D patients but not in the
AITDw/oT1D patients. In genotypes combining the DRB1-DQB1 haplotypes susceptible to T1D, only DR4/DR8 was signifi-cantly more frequent compared to the controls. We classified the haplotypes into three types (susceptible [S], protective [P]
and neutral [N]) to examine their association with T1D development. Compared to the controls, the genotypes S/S and N/P
were observed more and less frequently, respectively, in AITD+T1D. No difference in the frequency of those genotypes
between AITDw/oT1D and controls was observed.
Conclusions:The risk of the future development of T1D in Japanese patients with AITD could be stratified by an analysis of
combinations of HLA DRB1-DQB1 haplotypes.
