HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations
Al Yafei Z. Mack S.J. Alvares M. Ali B.R. Afandi B. Beshyah S.A. Sharma C. Osman W. Mirghani R. Nasr A. Al Remithi S. Al Jubeh J. Almawi W.Y. AlKaabi J. ElGhazali G.
24 March 2022Frontiers Media S.A.
Frontiers in Genetics
2022#13
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. Copyright
Emiratis , ethnicity , haplotypes , HLA , type 1 diabetes
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Sheikh Khalifa Medical City, Purehealth, Abu Dhabi, United Arab Emirates
Department of Pediatrics, University of California, San Francisco, CA, United States
Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
Department of Internal Medicine, Tawam Hospital, Al Ain, United Arab Emirates
Department of Medicine, Dubai Medical College, Dubai, United Arab Emirates
Department of Internal Medicine, United Arab Emirates University, Al Ain, United Arab Emirates
College of Arts and Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
Higher College of Technology, Abu Dhabi, United Arab Emirates
Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan
Sheikh Khalifa Medical City
Department of Pediatrics
Department of Genetics and Genomics
Department of Internal Medicine
Department of Medicine
Department of Internal Medicine
College of Arts and Sciences
Higher College of Technology
Department of Basic Medical Sciences
Department of Biomedical Sciences
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