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 x 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 x 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 alpha/beta 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 a/b 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.