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

Diabetes Metab Res Rev. 2011 Nov;27(8):899-905. doi: 10.1002/dmrr.1270.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Autoantibodies / analysis
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Body Mass Index
  • Case-Control Studies
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / immunology
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / immunology
  • HLA-A Antigens / genetics*
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / physiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / genetics
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • Cation Transport Proteins
  • HLA-A Antigens
  • HLA-DRB1 Chains
  • ICA512 autoantibody
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • PTPRN protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase