约旦人 1 型糖尿病与 HLA-DRB1 和 -DQ 等位基因及单体型的关联。

Association of HLA-DRB1 and -DQ Alleles and Haplotypes with Type 1 Diabetes in Jordanians.

机构信息

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.

Diabetes Center, King Abdullah University Hospital, P.O.Box 630001, Irbid 21110, Jordan.

出版信息

Endocr Metab Immune Disord Drug Targets. 2020;20(6):895-902. doi: 10.2174/1871530319666191119114031.

DOI:10.2174/1871530319666191119114031

PMID:31742498

Abstract

BACKGROUND

The Human Leukocyte Antigen (HLA) class II genes, particularly the HLADR and -DQ loci, have been shown to play a crucial role in Type 1 Diabetes (T1D) development.

OBJECTIVE

This study is the first to examine the contribution of the HLA-DR/DQ alleles and haplotypes to T1D susceptibility in Jordanians.

METHODS

Polymerase chain reaction sequence-specific primers (PCR-SSP) were used to genotype 41 Jordanian healthy controls and 50 insulin-dependent diabetes mellitus (IDDM) patients.

RESULTS

The following alleles were found to be significant high risk alleles in T1D Jordanian patients: DRB104 (OR=3.95, p<0.001), DRB10301(OR=5.27, p<0.001), DQA10301 (OR=5.67, p<0.001), DQA10501(OR=3.18, p=0.002), DQB10201(OR=2.18, p=0.03), DQB10302 (OR=5.67, p<0.001). However, Jordanians harboring the DRB10701 (OR=0.37, p=0.01), DRB11101 (OR=0.2, p=0.01), DQA10505 (OR=0.31, p=0.02), DQA10103 (OR=0.33, p=0.04), DQA10201 (OR=0.45, p=0.04), DQB10301 (OR=0.23, p=0.001), DQB1*0501 (OR=0.18, p=0.009) alleles had a significantly lower risk of developing T1D.

CONCLUSION

A strong positive association of DRB104-DQA10301-DQBl0302 (OR=5.67, p<0.001) and DRB10301-DQA10501-DQB10201 (OR=6.24, p<0.001) putative haplotypes with IDDM was evident in Jordanian IDDM patients whereas DRB11101-DQA10505- DQB1*0301 (OR=0.23, p=0.03) was shown to have a protective role against T1D in Jordanians. Our findings show that specific HLA class II alleles and haplotypes are significantly associated with susceptibility to T1D in Jordanians.

摘要

背景

人类白细胞抗原（HLA）II 类基因，特别是 HLA-DR 和-DQ 基因座，已被证明在 1 型糖尿病（T1D）的发展中起着至关重要的作用。

目的

本研究首次探讨了 HLA-DR/DQ 等位基因和单倍型对约旦人 T1D 易感性的影响。

方法

采用聚合酶链反应序列特异性引物（PCR-SSP）对 41 名约旦健康对照者和 50 名胰岛素依赖型糖尿病（IDDM）患者进行基因分型。

结果

在 T1D 约旦患者中，以下等位基因被发现是显著的高风险等位基因：DRB104（OR=3.95，p<0.001），DRB10301（OR=5.27，p<0.001），DQA10301（OR=5.67，p<0.001），DQA10501（OR=3.18，p=0.002），DQB10201（OR=2.18，p=0.03），DQB10302（OR=5.67，p<0.001）。然而，约旦人携带 DRB10701（OR=0.37，p=0.01），DRB11101（OR=0.2，p=0.01），DQA10505（OR=0.31，p=0.02），DQA10103（OR=0.33，p=0.04），DQA10201（OR=0.45，p=0.04），DQB10301（OR=0.23，p=0.001），DQB1*0501（OR=0.18，p=0.009）等位基因的 T1D 发病风险显著降低。

结论

在约旦的 IDDM 患者中，DRB104-DQA10301-DQB10302（OR=5.67，p<0.001）和 DRB10301-DQA10501-DQB10201（OR=6.24，p<0.001）假定单倍型与 IDDM 之间存在强烈的正关联，而 DRB11101-DQA10505-DQB1*0301（OR=0.23，p=0.03）则显示对 T1D 具有保护作用。我们的研究结果表明，特定的 HLA Ⅱ类等位基因和单倍型与约旦人 T1D 的易感性显著相关。