title: Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes.
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.
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Yong
authors: Y
authors: Gu
authors: Mei
authors: M
authors: Zhang
authors: Heng
authors: H
authors: Chen
authors: Zhixiao
authors: Z
authors: Wang
authors: Chunyan
authors: C
authors: Xing
authors: Hui
authors: H
authors: Yang
authors: Xinyu
authors: X
authors: Xu
authors: Yu
authors: Y
authors: Liu
authors: Zhiguang
authors: Z
authors: Zhou
authors: Liping
authors: L
authors: Yu
authors: John
authors: J
authors: Hutton
authors: George
authors: G
authors: Eisenbarth
authors: Tao
authors: T
authors: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001323:Autoantibodies / Q000032:analysis / Q000097:blood* / Q000276:immunology; D015992:Body Mass Index; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase