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  • Title: Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes.
    Author: Gu Y, Zhang M, Chen H, Wang Z, Xing C, Yang H, Xu X, Liu Y, Zhou Z, Yu L, Hutton J, Eisenbarth G, Yang T.
    Journal: Diabetes Metab Res Rev; 2011 Nov; 27(8):899-905. PubMed ID: 22069282.
    Abstract:
    BACKGROUND: To reveal the aetiology of diabetes, the relationships between the islet autoantibodies, human leukocyte antigen (HLA)-A and DRB1 genotypes in the Chinese patients with type l diabetes (T1D) were investigated in our study. METHODS: In the cross-sectional and case-control study, peripheral blood samples were collected from 600 T1D patients and 102 healthy controls. The genetic polymorphisms of HLA-A and DRB1 are examined with polymerase chain reaction-sequence oligonucleotide probe method. The zinc transporter 8 antibody (ZnT8A), glutamic acid decarboxylase antibody (GADA) and protein-tyrosine-phosphatase-2 autoantibody (IA2A) were detected by radioligand assay. RESULTS: The A*2402, DRB1*0301, DRB1*0405 and DRB1*0901 alleles, and A*1101-DRB1*0901, A*2402-DRB1*0405 and A*2402-DRB1*0901 haplotypes were associated with T1D (all p<0.05). The positive rates of ZnT8A in patients carried DRB1*0901, IA2A in patients carried DRB1*0405 and A*1101-DRB1*0901 and GADA in patients carried DRB1*0901 and A*2402-DRB1*0901 were significantly higher than those not carried (p<0.05). HLA-DRB1*0901 was the independent risk factor of positive antibody in T1D patients. In addition, higher body mass index is also related with the loss of islet function besides high-risk HLA gene and islet autoantibody (p<0.05). CONCLUSIONS: The discordant association of autoantibodies with high-risk HLA gene may indicate the different immunology mechanisms of those autoantibodies. And metabolic burden resulting from overweight may accelerate apoptosis of beta cells.
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