Diverse human leukocyte antigen association of type 1 diabetes in north India.

Publisher: Blackwell Publishing Asia Country of Publication: Australia NLM ID: 101504326 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1753-0407 (Electronic) Linking ISSN: 17530407 NLM ISO Abbreviation: J Diabetes Subsets: MEDLINE

Original Publication: Richmond, Vic. : Blackwell Publishing Asia, 2009-

Genetic Predisposition to Disease*; Biomarkers/*analysis ; Diabetes Mellitus, Type 1/*genetics ; HLA Antigens/*genetics ; Histocompatibility Antigens Class I/*genetics ; Histocompatibility Antigens Class II/*genetics; Case-Control Studies ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/pathology ; Gene Frequency ; Haplotypes ; Humans ; India/epidemiology ; Prognosis

Background: Type 1 diabetes (T1D) is a complex disease, with involvement of various susceptibility genes. Human leukocyte antigen (HLA) on chromosome 6p21 is major susceptibility region. This study examined genetic association of HLA genes with T1D.
Methods: The study recruited 259 T1D patients and 706 controls from north India. PCR-SSP and LiPA were used to type HLA Class I and II alleles.
Results: At HLA Class I locus, HLA-A*02, A*26, B*08 and B*50 were significantly increased in patients vs controls (39.8% vs 28.9% [Bonferroni-corrected P {P c } = 0.032], 24.7% vs 9.6% [P c  = 4.83 × 10 ^-8 ], 37.2% vs 15.7% [P c  = 1.92 × 10 ^-9 ], and 19.4% vs 5.5% [P c  = 4.62 × 10 ^-9 ], respectively). Similarly, in Class II region, DRB1*03 showed a strong positive association with T1D (78.7% vs 17.5% in controls; P = 1.02 × 10 ^-9 ). Association of DRB1*04 with T1D (28.3% vs 15.5% in controls; P c  = 3.86 × 10 ^-4 ) was not independent of DRB1*03. Negative associations were found between T1D and DRB1*07, *11, *13, and *15 (13.8% vs 26.1% in controls [P c  = 0.00175], 3.9% vs 16.9% in controls [P c  = 6.55× 10 ^-6 ], 5.5% vs 21.6% in controls [P c  = 2.51 × 10 ^-7 ], and 16.9% vs 43.9% in controls [P c  = 9.94× 10 ^-10 ], respectively). Compared with controls, patients had significantly higher haplotype frequencies of A*26-B*08-DRB1*03-DQA1*05-DQB1*02 (10.43% vs 1.96%; P = 7.62 × 10 ^-11 ), A*02-B*50-DRB1*03-DQA1*05-DQB1*02 (6.1% vs 0.71%; P = 2.19 × 10 ^-10 ), A*24-B*08-DRB1*03-DQA1*05-DQB1*02 (4.72% vs 0.8%; P = 5.4 × 10 ^-7 ), A*02-B*08-DRB1*03-DQA1*05-DQB1*02 (2.36% vs 0.18%; P = 3.6 × 10 ^-5 ), and A*33-B*58-DRB1*03-DQA1*05-DQB1*02 (4.33% vs 1.25%; P = 0.00019).
Conclusions: In north India, T1D is independently associated only with HLA-DRB1*03 haplotypes, and is negatively associated with DRB1*07, *11, *13, and *15.
(© 2019 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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Department of Biotechnology, Ministry of Science and Technology, Science and Engineering Research Board, Government of India; Indian Council of Medical Research

Keywords: 1型糖尿病; association; human leukocyte antigen; north India; type 1 diabetes; 人类白细胞抗原; 印度北部; 相关性
Local Abstract: [Publisher, Chinese] 摘要: 背景 1型糖尿病(T1D)是一种复杂的疾病, 涉及多种易感基因。6p21染色体上的人类白细胞抗原(Human leukocyte antigen, HLA)是主要的易感区域。本研究调查了HLA基因与T1D之间的遗传相关性。 方法 本研究在印度北部招募了259名T1D患者与706名对照者。使用PCR-SSP与LiPA来测定HLA I类与II类等位基因。 结果 在HLA I类位点, T1D患者组的HLA-A*02、A*26、B*08以及B*50与对照组相比均显著增加(分别为39.8%与28.9% [Bonferroni校正P值{P c } = 0.032]、24.7%与9.6%[Pc = 4.83×10 ⁻⁸ ]、37.2%与15.7% [Pc = 1.92×10 ⁻⁹ ]、以及19.4%与5.5%[Pc = 4.62×10 ⁻⁹ ])。同样, 在HLA II类区域, 发现DRB1*03与T1D之间具有强烈的正相关(78.7%, 对照组为17.5%；P = 1.02×10 ⁻⁹ )。DRB1*04与T1D之间的相关性(28.3%, 对照组为15.5%；P c = 3.86×10 ⁻⁴ )依赖于DRB1*03。发现T1D与DRB1*07、*11、*13以及*15之间呈负相关(分别为13.8%, 对照组为26.1%[P c = 0.00175]；3.9%, 对照组为16.9%[P c = 6.55×10 ⁻⁶ ]；5.5%, 对照组为21.6%[P c = 2.51×10 ⁻⁷ ]以及16.9%, 对照组为43.9%[P c = 9.94×10 ⁻¹⁰ ])。与对照组相比, T1D患者的A*26-B*08-DRB1*03-DQA1*05-DQB1*02(10.43%与1.96%；P = 7.62×10 ⁻¹¹ )、A*02-B*50-DRB1*03-DQA1*05-DQB1*02(6.1%与0.71%；P = 2.19×10 ⁻¹⁰ )、A*24-B*08-DRB1*03-DQA1*05-DQB1*02(4.72%与0.8%；P = 5.4×10 ⁻⁷ )、A*02-B*08-DRB1*03-DQA1*05-DQB1*02(2.36%与0.18%；P = 3.6×10 ⁻⁵ )以及A *33-B*58-DRB1*03-DQA1*05-DQB1*02(4.33%与1.25%；P = 0.00019)单倍型频率明显更高。 结论 在印度北部, T1D仅与HLADRB1*03单倍型独立相关, 并且与DRB1*07、*11、*13以及*15之间呈负相关。.

0 (Biomarkers)
0 (HLA Antigens)
0 (Histocompatibility Antigens Class I)
0 (Histocompatibility Antigens Class II)

Date Created: 20190108 Date Completed: 20200312 Latest Revision: 20200312

20250114

10.1111/1753-0407.12898

30614662