Diverse human leukocyte antigen association of type 1 diabetes in north India
印度北部人群多种白细胞抗原与1型糖尿病的相关性
Funding information Department of Biotechnology, Ministry of Science and Technology, Science and Engineering Research Board, Government of India; Indian Council of Medical Research
Abstract
enBackground
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 {Pc} = 0.032], 24.7% vs 9.6% [Pc = 4.83 × 10−8], 37.2% vs 15.7% [Pc = 1.92 × 10−9], and 19.4% vs 5.5% [Pc = 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; Pc = 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 [Pc = 0.00175], 3.9% vs 16.9% in controls [Pc = 6.55× 10−6], 5.5% vs 21.6% in controls [Pc = 2.51 × 10−7], and 16.9% vs 43.9% in controls [Pc = 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.
Abstract
zh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{Pc} = 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%；Pc = 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%[Pc = 0.00175]；3.9%, 对照组为16.9%[Pc = 6.55×10−6]；5.5%, 对照组为21.6%[Pc = 2.51×10−7]以及16.9%, 对照组为43.9%[Pc = 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。
CONFLICTS OF INTEREST
The authors have no conflicts of interest to disclose.
