Open AccessHLA ‐A*33‐ DR 3 and A*33‐ DR 9 haplotypes enhance the risk of type 1 diabetes in Han Chinese
Author(s) -
Zhang Juanjuan,
Zhao Liebin,
Wang Bokai,
Gao Jie,
Wang Li,
Li Li,
Cui Bin,
Hu Min,
Hong Jie,
Gu Weiqiong,
Wang Weiqing,
Ning Guang
Publication year - 2016
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12462
Subject(s) - medicine , haplotype , odds ratio , type 2 diabetes , human leukocyte antigen , diabetes mellitus , immunology , type 1 diabetes , gastroenterology , microbiology and biotechnology , antigen , endocrinology , genotype , genetics , gene , biology
Abstract 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‐ DR 3 and A33‐ DR 9 haplotypes significantly enhanced the risk of type 1 diabetes (A33‐ DR 3 , odds ratio 5.1 [2.40–10.78], P = 4.0 × 10 −6 ; A33‐ DR 9 , odds ratio 13.0 [1.69–100.32], P = 0.004). In type 1 diabetic patients, compared with A33‐ DR 3 ‐negative carriers, A33‐ DR 3 ‐positive carriers had significantly lower percentages of CD 3 + CD 4 + T cells (42.5 ± 7.72 vs 37.0 ± 8.35%, P = 0.023), higher percentages of CD 3 + CD 8 + 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 CD 4/ CD 8 ratios (1.71 ± 0.75 vs 1.16 ± 0.35, P = 0.003). Conclusions It is the first time that the haplotypes A33‐ DR 3 and A33‐ DR 9 were found with an enhanced predisposition to type 1 diabetes in Han Chinese. A33‐ DR 3 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.