HLA-DRB1 and -DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations.

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 and alleles, genotypes, and haplotypes with T1D in United Arab Emirates. Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were and genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package. In total, 15 and 9 alleles were identified in the study subjects, of which the association of and , and with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified [0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33-5.1), = 3.48 × 10]; [0.077 vs. 0.014, OR = 6.06 (2.03-24.37), = 2.3 × 10] and [0.060 vs. 0.010, OR = 6.24 (1.79-33.34), = 0.011] as positively associated, and [0.024 vs. 0.075, OR = 0.3 (0.11-0.74), = 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for [0.104 vs. 0.006, OR = 25.03 (8.23-97.2), = 2.6 × 10], followed by [0.094 vs. 0.010, OR = 8.72 (3.17-25.32), = 3.18 × 10] diplotypes. While and 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 and and T1D across different populations.