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.