DataSheet1_HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations.docx

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.

背景：HLA II 类（DR 和 DQ）等位基因和抗原在历史上表现出对1型糖尿病（T1D）的强烈遗传易感性。本研究评估了DRB1和DQB1等位基因、基因型和单倍型与阿拉伯联合酋长国1型糖尿病的关联。材料与方法：研究对象包括149名1型糖尿病患者和147名血糖正常的对照组。病例和对照均为阿拉伯人，并使用基于序列的分型对HLA-DRB1和-DQB1进行了基因分型。统计分析采用Bridging Immunogenomic Data-Analysis Workflow Gaps R包进行。结果：在研究对象中，共鉴定出15个DRB1和9个DQB1等位基因，其中DRB1*03:01、DRB1*04:02、DRB1*11:01、DRB1*16:02与DQB1*02:01、DQB1*03:02、DQB1*03:01和DQB1*06:01的关联在多重比较校正后仍然存在。二位点单倍型分析发现，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]和DRB1*04:05∼DQB1*03:02 [0.060 vs. 0.010，OR = 6.24（1.79–33.34），Pc = 0.011]与T1D呈正相关，而DRB1*16:02∼DQB1*05:02 [0.024 vs. 0.075，OR = 0.3（0.11–0.74），Pc = 0.041]与T1D呈负相关，经Bonferroni校正后得出。此外，DR3/DR4 [0.104 vs. 0.006，OR = 25.03（8.23–97.2），Pc = 2.6 × 10−10]和DR3/DR3 [0.094 vs. 0.010，OR = 8.72（3.17–25.32），Pc = 3.18 × 10−8]双等位基因型显示出最高的T1D风险。结论：虽然与阿拉伯人群中的T1D相关的DRB1和DQB1等位基因和单倍型与高加索人和非高加索人群相似，但在欧洲、非洲和亚洲人群中与T1D相关的几个等位基因和单倍型并未观察到。这强调了种族多样性和不同人群中DRB1与DQB1与T1D之间可能存在的多样关联的贡献。