Diverse human leukocyte antigen 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 {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.

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring.

Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.