Highlights• Type 1 diabetes (T1D) in north India is strongly associated with HLA-DRB1*03 haplotypes. • The association between HLA-DRB1*04 and T1D in north India differs from that in south India and in Caucasians. AbstractBackground: 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

The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between β-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1 ∗ 03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA– (91.41% vs. 66.13%, Bonferroni- corrected   P   P c = 1.11 × 10 − 5 ; OR = 5.45 ; 95% CI: 2.67-11.08). Similarly, HLA-DQB1 ∗ 02 was found to be significantly increased in GADA+ patients (94.53%, P c = 2.19 × 10 − 5 ; OR = 6.27 ; 95% CI: 2.7-14.49) as compared to GADA– (73.39%). The frequencies of HLA-DRB1 ∗ 04 and DQB1 ∗ 03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A– (25.94% and 33.96%, respectively). Further, the frequency of DRB1 ∗ 03-DQB1 ∗ 02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P = 3.94 × 10 − 5 ; OR = 2.13 ; 95 % CI = 1.49 -3.03). Similarly, HLA-DRB1 ∗ 04-DQB1 ∗ 03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A– patients (22.5% vs. 12.97%; P = 0.041 ; OR = 1.95 ; 95 % CI = 1.08 -3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1 ∗ 03/DQB1 ∗ 02 and HLA-DRB1 ∗ 04/DQB1 ∗ 03 might play an important role in the development of GADA and IA2A, respectively.