一个扩展的HLA-DQ-DR单倍型而非单独的DRB1基因，对类风湿关节炎易感性起作用。

An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition.

作者信息

Zanelli E, Huizinga T W, Guerne P A, Vischer T L, Tiercy J M, Verduyn W, Schreuder G M, Breedveld F C, de Vries R R

机构信息

Department of Immunohaematology and Blood Bank, Leiden University Medical Centre, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.

出版信息

Immunogenetics. 1998 Nov-Dec;48(6):394-401. doi: 10.1007/s002510050450.

DOI:10.1007/s002510050450

PMID:9799335

Abstract

In the present study, we tested our hypothesis on the role of a DQ-DR haplotype in rheumatoid arthritis (RA) predisposition. Using two groups of patients and controls, one from The Netherlands and one from Switzerland, we found that DQA10301-homozygous and DQA10301//DQA10101/04-heterozygous individuals are highly predisposed to RA in both populations, while DQA10101/04-homozygous are not. The DQA10301-DRB10403/06/07 and DQA10301-DRB10901 haplotypes are not associated with RA by themselves but strongly increase the risk of developing disease in DQA10301- and DQA10101/04-heterozygous. DRB1 alleles carrying the motif DERAA in their third hypervariable region, i.e., *0103, *0402, *1102, *1103, 1301, and 1302, provide a long-lasting protection against RA in DQA10101/04- but not in DQA10301-positive individuals. These data show that considering both DQ and DR gives a better distinction between patients and controls than the shared epitope hypothesis.

摘要

在本研究中，我们检验了关于DQ-DR单倍型在类风湿关节炎（RA）易感性中作用的假设。我们使用了两组患者和对照组，一组来自荷兰，另一组来自瑞士，发现DQA10301纯合子个体以及DQA10301//DQA10101/04杂合子个体在这两个人群中都高度易患RA，而DQA10101/04纯合子个体则不然。DQA10301-DRB10403/06/07和DQA10301-DRB10901单倍型本身与RA无关，但会显著增加DQA10301和DQA10101/04杂合子个体患RA的风险。在其第三个高变区携带基序DERAA的DRB1等位基因，即*0103、*0402、1102、1103、1301和1302，能为DQA10101/04阳性个体提供长期的RA保护，但对DQA10301阳性个体则不然。这些数据表明，综合考虑DQ和DR比共享表位假设有助于更好地区分患者和对照。