Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 P387 | DOI: 10.1530/endoabs.35.P387

ECE2014 Poster Presentations Diabetes (epidemiology, pathophysiology) (63 abstracts)

The HLA-A*33 haplotype enhances the risk of type 1 diabetesin ndividuals with HLA-DR3+ or DR9+ haplotype

Juanjuan Zhang , Weiqiong Gu , Bokai Wang , Jie Gao , Li Li , Bin Cui , Jie Hong , Weiqing Wang & Guang Ning


Department of Endocrine and Metabolic diseases, Ruijin Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China.


Background: To investigate the typing for HLA-I in Chinese patients with type 1 diabetes (T1D) as a complement screening for HLA-II.

Methods: A total of 212 T1D patients and 200 healthy controls were enrolled. The genetic polymorphisms of HLA-I and II were examined with a high-resolution polymerase chain reaction-sequence-based typing method.

Results: The novel haplotype, A*33:03-B*58:01-C*03:02(A33), was associated with T1D (P<0.001, OR 3.2(1.738–5.843)). The A33 haplotype significantly enhanced the risk of T1D with specific HLA-DR/DQ haplotypes (DR3, OR 5.1(2.40–10.78)), P<0.001; DR9, OR 13.0(1.69–100.32), P=0.004). Compared to A33-DR3-negative carriers, A33-DR3-positive carriers had significantly lower percentages of CD3+CD4+T cells (42.5±7.72 vs 37.0±8.35%, P=0.011), higher percentages of CD3+CD8+T cells (27.4±7.09 vs 32.8±5.98%, P=0.003), CD45RA+CD62L+T cells (43.2±14.15 vs 50.5±9.75%, P=0.042) and TCRα/β T cells (70.0±7.00 vs 73.6±6.25%, P=0.037), and lower CD4/CD8 ratios (1.71±0.75 vs 1.16±0.35, P<0.001).

Conclusion: A novel haplotype A33 was found with enhanced predisposition to T1D for DR3 or DR9 carriers. A33-DR3 was associated with a striking reduction in the helper-to-cytotoxic cell ratio and preferential stimulation of ‘naive’ T cell and regulatory T cell. The typing for HLA-I and its immunogenic effects are important for more accurate HLA-II haplotype risk prediction and etiologic research in T1D patients.

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