Genetic epidemiology of type 1 diabetes mellitus in Taiwan

Some environmental and genetic factors play important roles in etiopathogen esis of type 1 or insulin-dependent diabetes mellitus (IDDM). HLA genes, th e IDDM1 locus located the human chromosome 6, were found to be associated w ith insulin-dependent diabetes mellitus. However, the incidence of IDDM var ied greatly among various populations. To evaluate the pathogenetic factors contributing to the development of IDDM in Taiwan, HLA typing was performe d in a group of IDDM unrelated individuals and IDDM pedigrees along with th e normal controls from the northern Taiwan. DNA genotypes of class II HLA w ere done by polymerase-chain-reaction based oligotyping techniques. We conf irmed that class II HLA genes were significantly associated with IDDM in Ta iwan. To study detailed molecular structure of class II HLA molecules and d isease association, we examined several amino acid residues on DQ alpha and DQ beta chains and the molecular mechanisms to explain the heterozygotic e ffect of the DR3/DR4 and DR3/DR9 in the Chinese population. Linkage analysi s in our pedigrees confirmed the association between HLA and IDDM in popula tion association studies. Among the several class II alleles, a closer segr egation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB l*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-pr edisposing allele in Taiwanese. For IDDM2 (INS) region, association with ID DM was not found due to that more than 90% of the population carried class I alleles. In our collection of IDDM, we found few cases (2.4%) carried mit ochondrial DNA mutation. Our studies in Taiwanese confirm a multigenetic na ture for IDDM. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.