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.
Autoantibody epitopes to the smaller isoform of glutamate decarboxylase do not differ in Swedish and Japanese type 1 diabetes patients and may be associated with high-risk human leucocyte antigen class II alleles
