ASSOCIATION OF HLA-DR, DQ GENOTYPE WITH DIFFERENT BETA-CELL FUNCTIONSAT IDDM DIAGNOSIS IN JAPANESE CHILDREN

Japanese IDDM patients have been demonstrated to have unique and diffe rent HLA associations from white patients, To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM i n Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood- onset Japanese IDDM patients were examined by polymerase chain reactio n-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific pri mers (SSP), Of the 88 IDDM patients, 26 (29.5%) had DRB10405-DQA1*030 2-DQB10401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*030 3/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the pr esent study (X does not contain protective alleles), Clinical heteroge neity such as age distribution at onset, prevalence and serum level of anti-CAD antibodies (GADAb), and residual pancreatic beta-cell functi on after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9, The frequency of DR9-DQ9 genotype was significantly higher i n the younger (0-10 years) than in the older (11-16 years) age-group o f onset, but the frequency of DR4-DQ4 was higher in the older (11-16 y ears) age-group, Although no association of DR-DO genotypes with the p revalence and serum level of GADAb was found among newly diagnosed pat ients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4, While no difference in time course o f serum C-peptide (CPR) levels was detected between GADAb(+) and GADAb (-) patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients, The residual pancreatic beta-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at d iagnosis through 12-18 months after diagnosis, These results suggest t hat the DR9-DQ9 genotype may induce stronger autoimmune destructive re sponse (T-helper 1 function) against target beta-cells than the DR4-DQ 4 genotype does, Our findings may warrant further studies on the assoc iation of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-e ncoded susceptibility to IDDM.