HLA-DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high-risk DR/DQ haplotype
HLA-DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high-risk DR/DQ haplotype
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DOI：
10.1046/j.1365-2370.2003.00369.x
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发表时间：
2003-04-01
期刊：
影响因子：
--
通讯作者：
Tilanus, MG
中科院分区：
文献类型：
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作者：
Al-Hussein, KA;Rama, NR;Tilanus, MG
人类白细胞抗原（HLA）II类DQB 1 *0201/0202-DRB 1 *04基因型已被确定为沙特阿拉伯人群中1型糖尿病[胰岛素依赖型糖尿病（IDDM）]的易感基因（P = 0.0002;比值比= 0.67; 95%置信区间= 0.009-0.381）。在这项研究中，我们寻找一个因素在DPB 1基因座分析DPB 1多态性使用基于序列的分型在86个沙特的IDDM患者和对照组，所有携带HLA-DRB 1 *04/DQB 1 *02单倍型或已知的易感等位基因DQB 1 *0201/0202。DPB 1 *0401具有显著的保护作用，在50名对照受试者中的17名（55%）和36名携带DQB 1 *0201/0202等位基因的IDDM患者中的2名（5%）中观察到（P = 0.0012;比值比= 8.75;置信区间= 1.72-59.70）。我们的数据显示，即使在健康受试者中存在易感DQB 1 *02等位基因的情况下，DPB 1 *0401等位基因的频率也很高，这可能表明HLA等位基因的这种组合对1型糖尿病具有保护作用。这一发现支持了保护性HLA II类基因可以覆盖HLA-DQ易感性等位基因所赋予的风险的假设。应使用更大的对照受试者和患者队列进行进一步研究，以证实这一观察结果。
The human leukocyte antigen (HLA) class II DQB1*0201/0202-DRB1*04 genotype has been identified as predisposing to type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] in the Saudi Arabian population (P = 0.0002; odds ratio = 0.67; 95% confidence interval = 0.009-0.381). In this study, we searched for a factor at the DPB1 locus by analysing DPB1 polymorphism using sequence-based typing in 86 Saudi IDDM patients and control subjects, all carrying the HLA-DRB1*04/DQB1*02 haplotype or the known susceptibility allele DQB1*0201/0202. Significant protection was conferred by DPB1*0401, which was observed in 17 of 50 control subjects (55%) and 2 of 36 IDDM patients (5%) with the DQB1*0201/0202 allele (P = 0.0012; odds ratio = 8.75; confidence interval = 1.72-59.70). Our data showing a high frequency of the DPB1*0401 allele even in the presence of the predisposing DQB1*02 allele in healthy subjects may indicate a protective effect of this combination of HLA alleles against type 1 diabetes. This finding supports the hypothesis that protective HLA class II genes can override the risk conferred by HLA-DQ susceptibility alleles. Further studies using larger cohorts of control subjects and patients should be undertaken to confirm this observation.