Open Access印度北部人群多种白细胞抗原与1型糖尿病的相关性
Author(s) -
Kumar Neeraj,
Mehra Narinder K.,
Kanga Uma,
Kaur Gurvinder,
Tandon Nikhil,
Chuzho Neihenuo,
Mishra Gunja,
Neolia Shekhar C.
Publication year - 2019
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12898
Subject(s) - human leukocyte antigen , medicine , type 1 diabetes , allele , locus (genetics) , genetic predisposition , diabetes mellitus , bonferroni correction , immunology , gastroenterology , antigen , endocrinology , gene , genetics , disease , biology , statistics , mathematics
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.