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

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 A2402, DRB10301, DRB10405 and DRB10901 alleles, and A1101-DRB10901, A2402-DRB10405 and A2402-DRB10901 haplotypes were associated with T1D (all p<0.05). The positive rates of ZnT8A in patients carried DRB10901, IA2A in patients carried DRB10405 and A1101-DRB10901 and GADA in patients carried DRB10901 and A2402-DRB10901 were significantly higher than those not carried (p<0.05). HLA-DRB10901 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.