Diverse Human Leukocyte Antigen (HLA) association of Type 1 diabetes in North India.

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 x 10(-8)], 37.2% vs 15.7% [P-c = 1.92 x 10(-9)], and 19.4% vs 5.5% [P-c = 4.62 x 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 x 10(-9)). Association of DRB1*04 with T1D (28.3% vs 15.5% in controls; P-c = 3.86 x 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 = 6.55x 10(-6)], 5.5% vs 21.6% in controls [P-c = 2.51 x 10(-7)], and 16.9% vs 43.9% in controls [P-c = 9.94x 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 x 10(-11)), A*02-B*50-DRB1*03-DQA1*05-DQB1*02 (6.1% vs 0.71%; P = 2.19 x 10(-10)), A*24-B*08-DRB1*03-DQA1*05-DQB1*02 (4.72% vs 0.8%; P = 5.4 x 10(-7)), A*02-B*08-DRB1*03-DQA1*05-DQB1*02 (2.36% vs 0.18%; P = 3.6 x 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.