title: HLA-A*33-DR3 and A*33-DR9 haplotypes enhance the risk of type 1 diabetes in Han Chinese.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Liebin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Bokai
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Center for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.|Laboratory for Endocrine & Metabolic Diseases, Institute of Health Science, Shanghai JiaoTong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000328:Adult; D044466:Asian People; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen; C038988:HLA-DR9 antigen
keywords: Genetics; HLA-A*33; Type 1 diabetes