Stayoussef Mouna, Benmansour Jihen, Al-Irhayim Abdul-Qader, Said Hichem B, Rayana Chiheb B, Mahjoub Touhami, Almawi Wassim Y
Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Clin Vaccine Immunol. 2009 Aug;16(8):1146-50. doi: 10.1128/CVI.00105-09. Epub 2009 Jun 24.
Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility to type 1 diabetes (T1D), and susceptible alleles and haplotypes were implicated in the pathogenesis of T1D. This study investigated the heterogeneity in HLA class II haplotype distribution among Tunisian patients with T1D. This was a retrospective case control study done in Monastir in central Tunisia. The subjects comprised 88 T1D patients and 112 healthy controls. HLA-DRB1 and -DQB1 genotyping was done by PCR-sequence-specific priming. Significant DRB1 and DQB1 allelic differences were seen between T1D patients and controls; these differences comprised DRB1030101 and DQB10302, which were higher in T1D patients than in control subjects, and DRB1070101, DRB1110101, DQB1030101, and DQB1060101, which were lower in T1D patients than in control subjects. In addition, the frequencies of DRB1030101-DQB10201 and DRB1040101-DQB10302 were higher in T1D patients than in control subjects, and the frequencies of DRB1070101-DQB10201 and DRB1110101-DQB1030101 haplotypes were lower in T1D patients than in control subjects. Multiple logistic regression analysis revealed the positive association of DRB1030101-DQB10201 and DRB1040101-DQB10302 and the negative association of only DRB1070101-DQB10201 haplotypes with T1D. Furthermore, a significantly increased prevalence of DRB1030101-DQB10201 homozygotes was seen for T1D subjects than for control subjects. Our results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with T1D in Tunisians. The identification of similar and unique haplotypes in Tunisians compared to other Caucasians highlights the need for evaluating the contribution of HLA class II to the genetic susceptibility to T1D with regard to haplotype usage and also to ethnic origin and racial background.
人类白细胞抗原（HLA）II类基因与1型糖尿病（T1D）的遗传易感性有关，易感等位基因和单倍型与T1D的发病机制相关。本研究调查了突尼斯T1D患者中HLA II类单倍型分布的异质性。这是一项在突尼斯中部莫纳斯提尔进行的回顾性病例对照研究。研究对象包括88例T1D患者和112例健康对照。通过聚合酶链反应-序列特异性引物法进行HLA-DRB1和-DQB1基因分型。T1D患者与对照之间存在显著的DRB1和DQB1等位基因差异；这些差异包括DRB1030101和DQB10302，在T1D患者中的比例高于对照受试者，以及DRB1070101、DRB1110101、DQB1030101和DQB1060101，在T1D患者中的比例低于对照受试者。此外，DRB1030101-DQB10201和DRB1040101-DQB10302在T1D患者中的频率高于对照受试者，而DRB1070101-DQB10201和DRB1110101-DQB1030101单倍型在T1D患者中的频率低于对照受试者。多因素逻辑回归分析显示DRB1030101-DQB10201和DRB1040101-DQB10302与T1D呈正相关，仅DRB1070101-DQB10201单倍型与T1D呈负相关。此外，T1D受试者中DRB1030101-DQB10201纯合子的患病率显著高于对照受试者。我们的结果证实了特定的HLA-DR和-DQ等位基因及单倍型与突尼斯人T1D的相关性。与其他高加索人相比，突尼斯人相似和独特单倍型的鉴定突出了有必要评估HLA II类基因对T1D遗传易感性的贡献，包括单倍型使用情况以及种族起源和种族背景。
