Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes

作者:Gu, Yong; Zhang, Mei; Chen, Heng; Wang, Zhixiao; Xing, Chunyan; Yang, Hui; Xu, Xinyu; Liu, Yu; Zhou, Zhiguang; Yu, Liping; Hutton, John; Eisenbarth, George; Yang, Tao*
来源:DIABETES-METABOLISM RESEARCH AND REVIEWS, 2011, 27(8): 899-905.
DOI:10.1002/dmrr.1270

摘要

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.