Pathophysiology and pathogenesis of childhood-onset insulin-dependent diabetes mellitus (IDDM)

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1. HLA-DR, DQ beta genes and DQ alpha genes analysisWe analyzed HLA antigen genes in 146 patients with IDDM and 97 controls. The patients were divided into three groups, that is, group E, A, and S, depending on the age at onset and clinical course of the disease. We found significantly decreased frequency in DRB1 150X(D) in all diabetic groups, and increased in 0405(S), 0901(V) in groups in A and E.. Moreover, 0802(D) was significantly increased in group A. DQA1(301), DQB1(303), DRB1(901) genotype was found most susceptibility (RR=7.29 , 3.79, 2.82 in groups E, A, E respectively) in Japanese pat.2. CTLA-4 and NeuroD/BETA2 polymorphism associated with Japanese childhood IDDM patients.: We found the significant increase in G/G phenotype, decreas A/A phenotype in group E compared with control. The relationship between HLA DRB1 405 and 901 and CTLA-4 polymorphism was evaluated. Odds ratio(OR) in 0901(+) vs 0901(-) and 0910(+)/CTLA4(G+) vs 0910(-)/CTLA4(G-) as well as 504 was significantly increased in diabetic groups suggested the both genes are additive but independently for the development of IDDM in Japanese children. There was no significant diference in NeuroD/BETA2 polymorphism in Japanese children.3. Idenfication of nonsynonymous polymorphism in the superantigen(SPA)-coding region of IDDMK_<1,2>-22 and association with IDDM: We identified two nonsynony-mous A/G polymorphism at the 339- and 510- in the SPA-coding region of IDDM-K_<1,2>-22 retrovirus. We found significant G/G polymorphism at 510- in group E and G/A phenotype at 339- in group S. Future study will be necessary for conclusions.