Hajjej Abdelhafidh, Almawi Wassim Y, Stayoussef Mouna, Hattab Lasmar, Hmida Slama
Department of Immunogenetics, National Blood Transfusion Center, Tunis, Tunisia.
School of Pharmacy, Lebanese American University, Byblos, Lebanon.
Exp Clin Endocrinol Diabetes. 2019 Oct;127(10):653-662. doi: 10.1055/a-0754-5586. Epub 2018 Nov 14.
The molecular association of HLA class II with type 1 diabetes (T1DM) was investigated in Tunisian Arabs using 3 kinds of analyses. The first was a case-control association study, using Relative Predispositional Effects method, involved 137 T1DM cases and 258 control subjects. The second was family-based association-linkage study, using Transmission Disequilibrium Test, and covering 50 Tunisian families comprising 73 T1DM patients and 100 parents. The third was a wide correlation study between 4 DRB1 alleles (DRB103, 04, 11, 15) and T1DM in 52 countries, using Spearman's Rho. Results from Case-control and family-based association studies showed that DRB103 and DRB104 alleles predispose to T1DM in Tunisian Arabs. Conversely, only DRB111 was protective for T1DM. DRB104-DQB103 haplotype was consistently associated positively with T1DM; DRB103/DRB104 genotype had the highest risk of T1DM development. Compared to DRB103, HLA-DRB1*04 was associated with higher T1DM incidence. Thus, the contribution of HLA class II to T1DM genetic susceptibility must be evaluated with regards to specific HLA alleles, genotypes, and haplotypes, and also ethnic and racial background.
在突尼斯阿拉伯人中，采用三种分析方法研究了人类白细胞抗原（HLA）II类分子与1型糖尿病（T1DM）的分子关联。第一种是病例对照关联研究，采用相对易感性效应方法，涉及137例T1DM患者和258名对照受试者。第二种是基于家系的关联连锁研究，采用传递不平衡检验，涵盖50个突尼斯家庭，包括73名T1DM患者和100名父母。第三种是使用斯皮尔曼等级相关系数，在52个国家对4个DRB1等位基因（DRB103、04、11、15）与T1DM进行广泛的相关性研究。病例对照研究和基于家系的关联研究结果表明，DRB103和DRB104等位基因使突尼斯阿拉伯人易患T1DM。相反，只有DRB111对T1DM有保护作用。DRB104-DQB103单倍型始终与T1DM呈正相关；DRB103/DRB104基因型发生T1DM的风险最高。与DRB103相比，HLA-DRB1*04与更高的T1DM发病率相关。因此，必须根据特定的HLA等位基因、基因型和单倍型，以及种族和民族背景，评估HLA II类分子对T1DM遗传易感性的贡献。
