Department of Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Diabetes Metab Res Rev. 2020 Nov;36(8):e3345. doi: 10.1002/dmrr.3345. Epub 2020 Jun 15.
Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.
A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.
DRB103:01-DQA105:01-DQB102:01 (32.4%; OR = 3.68; P < .0001), DRB104:05-DQA103:02-DQB103:02 (6.6%; OR = 6.76; P < .0001), DRB104:02-DQA103:01-DQB103:02 (6.0%; OR = 3.10; P = .0194), DRB104:01-DQA103:01-DQB103:02 (3.7%; OR = 4.22; P = .0335), and DRB104:05-DQA103:02-DQB102:02 (2.7%; OR = 6.31; P = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB107:01-DQA102:01-DQB102:02 (OR = 0.41; P = .0001), DRB113:01-DQA101:03-DQB106:03 (OR = 0.05; P < .0001), DRB115:01-DQA101:02-DQB106:02 (OR = 0.03; P < .0001), and DRB111:01-DQA105:05-DQB103:01 (OR = 0.07; P = .0291) were significantly decreased. Homozygous DRB103:01-DQA105:01-DQB102:01 genotypes and combinations of DRB103:01-DQA105:01-DQB102:01 with DRB104:05-DQA103:02-DQB103:02, DRB104:02-DQA103:01-DQB103:02, and DRB104:01-DQA103:01-DQB103:02 were significantly increased in cases than controls. Combinations of DRB103:01-DQA105:01-DQB102:01 with DRB107:01-DQA102:01-DQB102:02 and DRB113:02-DQA101:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction.
HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.
1 型糖尿病（T1D）是一种影响全球许多儿童的自身免疫性疾病。遗传因素和环境触发因素在发病机制中起着至关重要的相互作用。本研究旨在评估 HLA-DRB1-DQA1-DQB1 等位基因、单倍型和基因型在沙特 T1D 患者中的风险贡献。
使用反向序列特异性寡核苷酸（rSSO）Lab Type high definition（HD）试剂盒，对 222 名 T1D 患儿和 342 名对照进行 HLA-DRB1、-DQA1 和-DQB1 基因分型。使用 SAS 统计软件包比较病例组和对照组之间的等位基因、单倍型和二倍型。
DRB103:01-DQA105:01-DQB102:01（32.4%；OR=3.68；P<.0001）、DRB104:05-DQA103:02-DQB103:02（6.6%；OR=6.76；P<.0001）、DRB104:02-DQA103:01-DQB103:02（6.0%；OR=3.10；P=.0194）、DRB104:01-DQA103:01-DQB103:02（3.7%；OR=4.22；P=.0335）和 DRB104:05-DQA103:02-DQB102:02（2.7%；OR=6.31；P=.0326）单倍型在病例组中显著增加，而 DRB107:01-DQA102:01-DQB102:02（OR=0.41；P=.0001）、DRB113:01-DQA101:03-DQB106:03（OR=0.05；P<.0001）、DRB115:01-DQA101:02-DQB106:02（OR=0.03；P<.0001）和 DRB111:01-DQA105:05-DQB103:01（OR=0.07；P=.0291）单倍型显著降低。DRB103:01-DQA105:01-DQB102:01 纯合基因型以及 DRB103:01-DQA105:01-DQB102:01 与 DRB104:05-DQA103:02-DQB103:02、DRB104:02-DQA103:01-DQB103:02 和 DRB104:01-DQA103:01-DQB103:02 的组合在病例组中显著增加。DRB103:01-DQA105:01-DQB102:01 与 DRB107:01-DQA102:01-DQB102:02 和 DRB113:02-DQA101:02-DQB1*06:04 的组合具有较低的 OR 值，但经 Bonferroni 校正后，其降低的显著性不再显著。
沙特 T1D 患者的 HLA-DRB1-DQA1-DQB1 等位基因、单倍型和二倍型与西方和中东人群观察到的没有明显不同，但与东亚人群有很大不同。
