Steenkiste A, Valdes A M, Feolo M, Hoffman D, Concannon P, Noble J, Schoch G, Hansen J, Helmberg W, Dorman J S, Thomson G, Pugliese A
Department of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Tissue Antigens. 2007 Apr;69 Suppl 1:214-25. doi: 10.1111/j.1399-0039.2006.00772.x.
The type 1 diabetes (T1D) component of the 13th International Histocompatibility Workshop (IHW) obtained microsatellite (msat) and human leukocyte antigen (HLA)-DR/DQ data on case/control and family samples through an international collaboration. The aim was to detect the effects of susceptibility loci on the HLA complex independent of the primary determinants in the class II region (HLA-DR/DQ). As part of the activity of the 14th International HLA and Immunogenetics Workshop (14th IHIWS), a T1D workshop was held to present analyses of the 13th IHW data and to discuss the current status of knowledge about the genetics of T1D. These data are now available online through dbMHC, a web-based resource established by the National Center for Biotechnology. Continuing work since the 13th IHW has resulted in published work showing heterogeneity of DR3 haplotypes in data sets from the 13th IHW and Human Biological Data Interchange (HBDI). In addition, we identified markers that define DRB11501 DQB10602 haplotypes conferring reduced protection from diabetes in a Swedish 13th IHW data set. Further analyses of the 13th IHW data set not only showed some significant results but also demonstrated extensive heterogeneity reminiscent of non-HLA genes. The haplotype analysis in HBDI families identified two msats with significant effects on susceptibility and statistically significant age of onset effects at class III markers that are not because of linkage disequilibrium, with class I alleles known to affect age of onset. The above studies underscore the importance of refining our understanding of susceptibility associated with genes in the HLA complex.
第13届国际组织相容性研讨会（IHW）的1型糖尿病（T1D）项目通过国际合作获取了病例/对照样本及家系样本的微卫星（msat）和人类白细胞抗原（HLA）-DR/DQ数据。其目的是检测易感性位点对HLA复合体的影响，而不考虑II类区域（HLA-DR/DQ）中的主要决定因素。作为第14届国际HLA与免疫遗传学研讨会（第14届IHIWS）活动的一部分，举办了一次T1D研讨会，以展示对第13届IHW数据的分析，并讨论T1D遗传学的当前知识状况。这些数据现已通过dbMHC在线获取，dbMHC是美国国家生物技术信息中心建立的一个基于网络的资源库。自第13届IHW以来的持续研究成果已发表，显示第13届IHW和人类生物学数据交换（HBDI）数据集中DR3单倍型的异质性。此外，我们在瑞典第13届IHW数据集中鉴定出了定义DRB11501 DQB10602单倍型的标记，这些单倍型对糖尿病的保护作用降低。对第13届IHW数据集的进一步分析不仅显示了一些显著结果，还证明了广泛的异质性，这让人联想到非HLA基因。对HBDI家系的单倍型分析确定了两个对易感性有显著影响的微卫星，以及在III类标记上有统计学显著意义的发病年龄效应，这并非由于连锁不平衡，而已知I类等位基因会影响发病年龄。上述研究强调了深化我们对与HLA复合体中基因相关的易感性理解的重要性。
