The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes
The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes
复制标题
DOI：
10.2337/diabetes.49.1.121
复制
发表时间：
2000-01-01
期刊：
影响因子：
7.7
通讯作者：
Erlich, HA
中科院分区：
文献类型：
--
作者：
Noble, JA;Valdes, AM;Erlich, HA
HLA-DPB 1基因型确定的样本来自269个多重高加索家庭从人类生物数据交换。DRB 1和DQB 1位点的特点，允许分配DPB 1等位基因的单倍型和连锁不平衡值的计算。几个DPB 1等位基因的频率显着不同的患者和受影响的家庭为基础的控制对象。有些差异可归因于与DR和DQ等位基因的连锁不平衡，而另一些则不是。在这些数据中，DPB 1 *0301和DPB 1 *0202等位基因是1型糖尿病的易感基因，不仅在单个等位基因的分析中，而且在基因型分析中。DPB 1 *0402似乎具有保护作用;然而，分层分析表明其保护作用仅针对DR 3单倍型。基因型分析表明DPB 1 *0401具有保护作用。为了增加统计功效，将DPB 1等位基因合并为三类：易感、中性和去除与DR-DQ的连锁不平衡效应后的保护性。这些池的分析表明，DPB 1主要影响易感性，而不是保护，1型糖尿病在一个占主导地位的方式。这种效应在具有除最高风险DR 3/DR 4-DQB 1 *0302基因型以外的基因型的患者中更明显。这些数据支持DPB 1基因座在赋予1型糖尿病易感性中的作用。
HLA-DPB1 genotypes were determined for samples from 269 multiplex Caucasian families from the Human Biological Data Interchange. DRB1 and DQB1 loci were also characterized, allowing assignment of DPB1 alleles to haplotypes and calculation of linkage disequilibrium values. Frequencies for several DPB1 alleles differed significantly between patients and affected family-based control subjects. Some differences were attributable to linkage disequilibrium with DR and DQ alleles, whereas others were not. DPB1*0301 and DPB1*0202 alleles are predisposing for type 1 diabetes in these data, not only in analyses of individual alleles, but also in genotype analyses. DPB1*0402 appears protective; however, stratification analysis indicates that its protective effect is specific for DR3 haplotypes. A protective role for DPB1*0401 is suggested by genotype analysis. For increased statistical power, DPB1 alleles were pooled into three categories: susceptible, neutral, and protective after removal of effects due to linkage disequilibrium with DR-DQ. Analysis of these pools suggests that DPB1 primarily affects susceptibility to, rather than protection from, type 1 diabetes in a dominant fashion. This effect is more apparent in patients with genotypes other than the highest risk DR3/DR4-DQB1*0302 genotype. These data support a role for the DPB1 locus in conferring susceptibility to type 1 diabetes.