Abstract
Background:
HLA class II (DR and DQ) alleles and antigens have historically shown strong genetic predisposition to type 1 diabetes (T1D). This study evaluated the association of
DRB1
and
DQB1
alleles, genotypes, and haplotypes with T1D in United Arab Emirates.
Materials and Methods:
Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were
HLA-DRB1
and
-DQB1
genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package.
Results:
In total, 15
DRB1
and 9
DQB1
alleles were identified in the study subjects, of which the association of
DRB1*03:01, DRB1*04:02, DRB1*11:01, DRB1*16:02,
and
DQB1*02:01, DQB1*03:02, DQB1*03:01
, and
DQB1*06:01
with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified
DRB1*03:01∼DQB1*02:01
[0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33–5.1),
Pc
= 3.48 × 10
−10
];
DRB1*04:02∼DQB1*03:02
[0.077 vs. 0.014, OR = 6.06 (2.03–24.37),
Pc
= 2.3 × 10
−3
] and
DRB1*04:05∼DQB1*03:02
[0.060 vs. 0.010, OR = 6.24 (1.79–33.34),
Pc
= 0.011] as positively associated, and
DRB1*16:02∼DQB1*05:02
[0.024 vs. 0.075, OR = 0.3 (0.11–0.74),
Pc
= 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for
DR3/DR4
[0.104 vs. 0.006, OR = 25.03 (8.23–97.2),
Pc
= 2.6 × 10
−10
], followed by
DR3/DR3
[0.094 vs. 0.010, OR = 8.72 (3.17–25.32),
Pc
= 3.18 × 10
−8
] diplotypes.
Conclusion:
While
DRB1
and
DQB1
alleles and haplotypes associated with T1D in Emiratis showed similarities to Caucasian and non-Caucasian populations, several alleles and haplotypes associated with T1D in European, African, and Asian populations, were not observed. This underscores the contribution of ethnic diversity and possible diverse associations between
DRB1
and
DQB1
and T1D across different populations.