Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives

J-P Wang, Z-G Zhou, J Lin, G Huang, C Zhang, L Yang, Y Yuan, H-F Zhou, M Zhou, C Hou, W-D Zhou, H Peng, W A Hagopian
Tissue Antigens 2007, 70 (5): 369-75
The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes was higher (P < 0.05-0.01) but DQA1*0102-DQB1*0602 haplotype was lower (P < 0.01) in T1D patients. DQA1*03 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA1*03-DQB1*0303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA1*0102-DQB1*0602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA1*03-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.

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