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

BACKGROUND: Type 1 Diabetes (T1D) is a complex disease with the involvement of various susceptibility genes. Human Leukocyte Antigen (HLA) on chromosome 6p21 is the major susceptibility region. This study examined the genetic association of HLA genes with T1D.

METHODS: The study recruited 259 T1D patients and 706 controls from North India. Genomic DNA was extracted from EDTA blood. HLA class I and II typing was carried out by polymerase chain reaction-sequence specific primers (PCR-SSP) and LiPA (Line Probe Assay).

RESULTS: At HLA class I locus, HLA-A*02, A*26, B*08 and B*50 were observed to be significantly increased in patients versus controls {(39.8% vs 28.9%, pc =0.032), (24.7% vs 9.6%, pc =4.83E-08), (37.2% vs 15.7%, pc = 1.92E-09) and (19.4% vs 5.5%, pc = 4.62E-09) respectively}. Similarly, at class II region DRB1*03 showed a strong positive association with the disease (78.7% vs 17.5% in controls, p=1.02E-09). Association of DRB1*04 with T1D (28.3% vs 15.5% in controls, pc = 3.86E-04) was not independent of DRB1*03. DRB1*07, *11, *13 and *15 showed a negative association with the disease {(13.8% vs 26.1%, pc = 0.00175), (3.9% vs 16.9%, pc = 6.55E-06), (5.5% vs 21.6%, pc = 2.51E-07) and (16.9% vs 43.9%, pc = 9.94E-10) respectively}. A*26-B*08-DRB1*03-DQA1*05-DQB1*02 (10.43% vs 1.96%, p=7.62E-11), A*02-B*50-DRB1*03-DQA1*05-DQB1*02 (6.1% vs 0.71%,p=2.19E-10), A*24-B*08-DRB1*03-DQA1*05-DQB1*02 (4.72% vs 0.8%, p=5.4E-07), A*02-B*08-DRB1*03-DQA1*05-DQB1*02 (2.36% vs 0.18%, p=3.6E-05) and A*33-B*58-DRB1*03-DQA1*05-DQB1*02 (4.33% vs 1.25%, p=0.00019) were found to be significantly increased in patients versus controls.

CONCLUSIONS: In North India, T1D is independently associated with only HLA-DRB1*03 haplotypes and negatively associated with DRB1*07, *11, *13 and *15.