Genetic epidemiology of type 1 diabetes mellitus in Taiwan.
Some environmental and genetic factors play important roles in etiopathogenesis of type 1 or insulin-dependent diabetes mellitus (IDDM). HLA genes, the IDDM1 locus located the human chromosome 6, were found to be associated with insulin-dependent diabetes mellitus. However, the incidence of IDDM varied greatly among various populations. To evaluate the pathogenetic factors contributing to the development of IDDM in Taiwan, HLA typing was performed in a group of IDDM unrelated individuals and IDDM pedigrees along with the normal controls from the northern Taiwan. DNA genotypes of class II HLA were done by polymerase-chain-reaction based oligotyping techniques. We confirmed that class II HLA genes were significantly associated with IDDM in Taiwan. To study detailed molecular structure of class II HLA molecules and disease association, we examined several amino acid residues on DQalpha and DQbeta chains and the molecular mechanisms to explain the heterozygotic effect of the DR3/DR4 and DR3/DR9 in the Chinese population. Linkage analysis in our pedigrees confirmed the association between HLA and IDDM in population association studies. Among the several class II alleles, a closer segregation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB1*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-predisposing allele in Taiwanese. For IDDM2 (INS) region, association with IDDM 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 mitochondrial DNA mutation. Our studies in Taiwanese confirm a multigenetic nature for IDDM.
Chuang
L
L
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. leeming@ha.mc.ntu.edu.tw
Tsai
S
S
Juang
J
J
Tsai
W
W
Tai
T
T
D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000276:immunology; D013624:Taiwan / Q000453:epidemiology
D001323:Autoantibodies; D006680:HLA Antigens; C096322:ICA512 autoantibody; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2