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

✍ Scribed by Yong Gu; Mei Zhang; Heng Chen; Zhixiao Wang; Chunyan Xing; Hui Yang; Xinyu Xu; Yu Liu; Zhiguang Zhou; Liping Yu; John Hutton; George Eisenbarth; Tao Yang


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
351 KB
Volume
27
Category
Article
ISSN
1520-7552

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✦ Synopsis


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. Copyright © 2011 John Wiley & Sons, Ltd.


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