HLA‐A*33‐DR3 and A*33‐DR9 haplotypes enhance the risk of type 1 diabetes in Han Chinese


AIMS/INTRODUCTION To investigate the typing for human leukocyte antigen (HLA) class I in Chinese patients with type 1 diabetes as a complement screening for HLA class II. MATERIALS AND METHODS A total of 212 type 1 diabetic patients and 200 healthy controls were enrolled. The genetic polymorphisms of HLA class I and II were examined with a high-resolution polymerase chain reaction sequence-based typing method. RESULTS The haplotype, A*33:03-B*58:01-C*03:02(A33), was associated with type 1 diabetes (P = 1.0 × 10(-4) , odds ratio 3.2 [1.738-5.843]). The A33-DR3 and A33-DR9 haplotypes significantly enhanced the risk of type 1 diabetes (A33-DR3, odds ratio 5.1 [2.40-10.78], P = 4.0 × 10(-6) ; A33-DR9, odds ratio 13.0 [1.69-100.32], P = 0.004). In type 1 diabetic patients, compared with 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 = 0.023), higher percentages of CD3(+) CD8(+) T cells (27.4 ± 7.09 vs 32.8 ± 5.98%, P = 0.005) and T-cell receptor α/β T cells (70.0 ± 7.00 vs 73.6 ± 6.25%, P = 0.031), and lower CD4/CD8 ratios (1.71 ± 0.75 vs 1.16 ± 0.35, P = 0.003). CONCLUSIONS It is the first time that the haplotypes A33-DR3 and A33-DR9 were found with an enhanced predisposition to type 1 diabetes in Han Chinese. A33-DR3 was associated with a reduction in the helper-to-cytotoxic cell ratio and preferential increase of T-cell receptor α/β T cell. The typing for HLA class I and its immunogenetic effects are important for more accurate HLA class II haplotype risk prediction and etiology research in type 1 diabetic patients.

DOI: 10.1111/jdi.12462

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@inproceedings{Zhang2016HA, title={ HLA‐A*33‐DR3 and A*33‐DR9 haplotypes enhance the risk of type 1 diabetes in Han Chinese}, author={Juanjuan Zhang and Liebin Zhao and Bokai Wang and Jie Gao and Li Wang and Li Li and Bin Cui and Min Hu and Jie Hong and Weiqiong Gu and Weiqing Wang and Guang Ning}, booktitle={Journal of diabetes investigation}, year={2016} }