HLA-A33-DR3 and A33-DR9 Haplotypes Enhance the Risk of Type 1 Diabetes in Han Chinese

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2016 May 17

PMID 27181214

Citations 6

Authors

Juanjuan Zhang

Liebin Zhao

Bokai Wang

Jie Gao

Li Wang

Li Li

Bin Cui

Min Hu

Jie Hong

Weiqiong Gu

Weiqing Wang

Guang Ning

Affiliations

Soon will be listed here.

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-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.

Citing Articles

The role of human leukocyte antigen in HTLV-1 infection and progression to ATLL and HAM/TSP: a systematic review and meta-analysis.

Mardi S, Rashidian M, Bastan F, Molaverdi G, Mozhgani S Virol J. 2025; 22(1):13.

PMID: 39833815 PMC: 11749399. DOI: 10.1186/s12985-024-02612-7.

The Association of Human Leukocyte Antigens Complex with Type 1 Diabetes in the Omani Population.

Al-Balushi M, Al-Badi S, Al-Yaarubi S, Al-Riyami H, Al-Shidhani A, Al-Hinai S Sultan Qaboos Univ Med J. 2023; 23(1):68-75.

PMID: 36865417 PMC: 9974035. DOI: 10.18295/squmj.2.2022.016.

HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes.

Jiang Z, Ren W, Liang H, Yan J, Yang D, Luo S Diabetologia. 2021; 64(9):2026-2036.

PMID: 34023962 PMC: 8382651. DOI: 10.1007/s00125-021-05476-6.

-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans.

Gaff J, Octaviana F, Pillay P, Ngassa Mbenda H, Ariyanto I, Gan J Int J Mol Sci. 2020; 21(2).

PMID: 31936167 PMC: 7014294. DOI: 10.3390/ijms21020380.

A pilot study of preproinsulin peptides reactivity in Chinese patients with type 1 diabetes.

Xian Y, Xu H, Gao Y, Yan J, Lv J, Ren W Diabetes Metab Res Rev. 2019; 36(2):e3228.

PMID: 31655017 PMC: 7027544. DOI: 10.1002/dmrr.3228.

References

Sarmiento L, Cabrera-Rode E, Lekuleni L, Cuba I, Molina G, Fonseca M . Occurrence of enterovirus RNA in serum of children with newly diagnosed type 1 diabetes and islet cell autoantibody-positive subjects in a population with a low incidence of type 1 diabetes. Autoimmunity. 2007; 40(7):540-5. DOI: 10.1080/08916930701523429. View

Kronenberg D, Knight R, Estorninho M, Ellis R, Kester M, de Ru A . Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill β-cells. Diabetes. 2012; 61(7):1752-9. PMC: 3379678. DOI: 10.2337/db11-1520. View

Pozzilli P, Tarn A, Schwarz G, Gale E, Bottazzo G . Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes. Diabetologia. 1989; 32(5):322-5. DOI: 10.1007/BF00265550. View

Juhela S, Hyoty H, Roivainen M, Harkonen T, Putto-Laurila A, Simell O . T-cell responses to enterovirus antigens in children with type 1 diabetes. Diabetes. 2000; 49(8):1308-13. DOI: 10.2337/diabetes.49.8.1308. View

Alford F, Henriksen J, Rantzau C, Vaag A, Hew L, Ward G . Impact of family history of diabetes on the assessment of beta-cell function. Metabolism. 1998; 47(5):522-8. DOI: 10.1016/s0026-0495(98)90234-7. View

Alper C, Larsen C, Dubey D, Awdeh Z, Fici D, Yunis E . The haplotype structure of the human major histocompatibility complex. Hum Immunol. 2006; 67(1-2):73-84. DOI: 10.1016/j.humimm.2005.11.006. View

Prelog M . Aging of the immune system: a risk factor for autoimmunity?. Autoimmun Rev. 2006; 5(2):136-9. DOI: 10.1016/j.autrev.2005.09.008. View

Degli-Esposti M, Leelayuwat C, Dawkins R . Ancestral haplotypes carry haplotypic and haplospecific polymorphisms of BAT1: possible relevance to autoimmune disease. Eur J Immunogenet. 1992; 19(3):121-7. DOI: 10.1111/j.1744-313x.1992.tb00051.x. View

Bassing C, Swat W, Alt F . The mechanism and regulation of chromosomal V(D)J recombination. Cell. 2002; 109 Suppl:S45-55. DOI: 10.1016/s0092-8674(02)00675-x. View

10.

Davis M, Bjorkman P . T-cell antigen receptor genes and T-cell recognition. Nature. 1988; 334(6181):395-402. DOI: 10.1038/334395a0. View

11.

Nejentsev S, Howson J, Walker N, Szeszko J, Field S, Stevens H . Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature. 2007; 450(7171):887-92. PMC: 2703779. DOI: 10.1038/nature06406. View

12.

Li X, Zhang X, Chen Y, Zhang K, Liu X, Li J . An analysis of HLA-A, -B, and -DRB1 allele and haplotype frequencies of 21,918 residents living in Liaoning, China. PLoS One. 2014; 9(4):e93082. PMC: 3972227. DOI: 10.1371/journal.pone.0093082. View

13.

Kumar N, Kaur G, Tandon N, Kanga U, Mehra N . Genomic evaluation of HLA-DR3+ haplotypes associated with type 1 diabetes. Ann N Y Acad Sci. 2013; 1283:91-6. DOI: 10.1111/nyas.12019. View

14.

. Effects of age, duration and treatment of insulin-dependent diabetes mellitus on residual beta-cell function: observations during eligibility testing for the Diabetes Control and Complications Trial (DCCT). The DCCT Research Group. J Clin Endocrinol Metab. 1987; 65(1):30-6. DOI: 10.1210/jcem-65-1-30. View

15.

Bland J, Altman D . Multiple significance tests: the Bonferroni method. BMJ. 1995; 310(6973):170. PMC: 2548561. DOI: 10.1136/bmj.310.6973.170. View

16.

Nakanishi K, Inoko H . Combination of HLA-A24, -DQA1*03, and -DR9 contributes to acute-onset and early complete beta-cell destruction in type 1 diabetes: longitudinal study of residual beta-cell function. Diabetes. 2006; 55(6):1862-8. DOI: 10.2337/db05-1049. View

17.

Diana J, Simoni Y, Furio L, Beaudoin L, Agerberth B, Barrat F . Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Nat Med. 2012; 19(1):65-73. DOI: 10.1038/nm.3042. View

18.

Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R . Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol. 2005; 54(Pt 9):879-883. DOI: 10.1099/jmm.0.46015-0. View

19.

. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2002; 26 Suppl 1:S5-20. DOI: 10.2337/diacare.26.2007.s5. View

20.

Graves P, Norris J, Pallansch M, Gerling I, Rewers M . The role of enteroviral infections in the development of IDDM: limitations of current approaches. Diabetes. 1997; 46(2):161-8. DOI: 10.2337/diab.46.2.161. View

HLA-A*33-DR3 and A*33-DR9 Haplotypes Enhance the Risk of Type 1 Diabetes in Han Chinese

HLA-A33-DR3 and A33-DR9 Haplotypes Enhance the Risk of Type 1 Diabetes in Han Chinese