AUTHOR=Al Yafei Zain , Mack Steven J. , Alvares Marion , Ali Bassam R. , Afandi Bachar , Beshyah Salem A. , Sharma Charu , Osman Wael , Mirghani Rajaa , Nasr Amre , Al Remithi Sareea , Al Jubeh Jamal , Almawi Wasim Y. , AlKaabi Juma , ElGhazali Gehad 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.841879

DOI=10.3389/fgene.2022.841879

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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 <italic>DRB1</italic> and <italic>DQB1</italic> alleles, genotypes, and haplotypes with T1D in United Arab Emirates.</p><p><bold>Materials and Methods:</bold> Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were <italic>HLA-DRB1</italic> and <italic>-DQB1</italic> genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package.</p><p><bold>Results:</bold> In total, 15 <italic>DRB1</italic> and 9 <italic>DQB1</italic> alleles were identified in the study subjects, of which the association of <italic>DRB1*03:01, DRB1*04:02, DRB1*11:01, DRB1*16:02,</italic> and <italic>DQB1*02:01, DQB1*03:02, DQB1*03:01</italic>, and <italic>DQB1*06:01</italic> with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified <italic>DRB1*03:01∼DQB1*02:01</italic> [0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33–5.1), <italic>Pc</italic> = 3.48 × 10<sup>−10</sup>]; <italic>DRB1*04:02∼DQB1*03:02</italic> [0.077 vs. 0.014, OR = 6.06 (2.03–24.37), <italic>Pc</italic> = 2.3 × 10<sup>−3</sup>] and <italic>DRB1*04:05∼DQB1*03:02</italic> [0.060 vs. 0.010, OR = 6.24 (1.79–33.34), <italic>Pc</italic> = 0.011] as positively associated, and <italic>DRB1*16:02∼DQB1*05:02</italic> [0.024 vs. 0.075, OR = 0.3 (0.11–0.74), <italic>Pc</italic> = 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for <italic>DR3/DR4</italic> [0.104 vs. 0.006, OR = 25.03 (8.23–97.2), <italic>Pc</italic> = 2.6 × 10<sup>−10</sup>], followed by <italic>DR3/DR3</italic> [0.094 vs. 0.010, OR = 8.72 (3.17–25.32), <italic>Pc</italic> = 3.18 × 10<sup>−8</sup>] diplotypes.</p><p><bold>Conclusion:</bold> While <italic>DRB1</italic> and <italic>DQB1</italic> 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 <italic>DRB1</italic> and <italic>DQB1</italic> and T1D across different populations.</p>