Seegers D, Borm M E A, van Belzen M J, Mulder C J J, Bailing J, Crusius J B A, Meijer J W R, Wijmenga C, Peña A S, Bouma G
Department of Immunogenetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Eur J Immunogenet. 2003 Dec;30(6):421-5. doi: 10.1111/j.1365-2370.2003.00428.x.
Celiac disease (CD) is a common gastro-intestinal disorder resulting from permanent intolerance to wheat gliadins and related proteins in rye and barley. In addition to the strong genetic association with HLA-DQ2 and HLA-DQ8, a genetic region on chromosomes 5 (CELIAC2) has been identified that harbours a susceptibility gene for CD. The gene(s) responsible for this association, however, remains to be identified. In the present study we evaluated polymorphisms in the genes encoding interleukin-12 p40 (IL12B) and interferon regulatory factor 1 (IRF1). Both genes are located in the celiac2 region, and have key roles in inducing interferon (IFN)-gamma secreting T helper 1 (Th1) cells, one of the immunological hallmarks of CD. The frequencies of a TaqI gene polymorphism in the 3' UTR of IL12B and a HinfI gene polymorphism in the 3' UTR of IRF1 were studied in 258 Dutch CD patients and 237 ethnically matched healthy controls. The transmission of the polymorphic variants from parents to affected child was determined in 123 families with at least one affected child. The frequencies of the IL12B TaqI gene polymorphism and the IRF1 HinfI gene polymorphism did not differ significantly between patients and controls. In addition, in the family study, no deviation from the expected transmission from parents to affected child of any of the polymorphic variants was found. The IL12B TaqI and the IRF1 HinfI gene polymorphisms do not appear to be involved in susceptibility to CD. Further studies on the factors that drive the Th1 immunopathology in CD are required.
乳糜泻（CD）是一种常见的胃肠道疾病，由对小麦醇溶蛋白以及黑麦和大麦中的相关蛋白质的永久性不耐受引起。除了与HLA - DQ2和HLA - DQ8有很强的遗传关联外，还在5号染色体上鉴定出一个遗传区域（CELIAC2），该区域含有一个CD易感基因。然而，负责这种关联的基因仍有待确定。在本研究中，我们评估了编码白细胞介素 - 12 p40（IL12B）和干扰素调节因子1（IRF1）的基因中的多态性。这两个基因都位于CELIAC2区域，并且在诱导分泌干扰素（IFN） - γ的辅助性T细胞1（Th1）中起关键作用，Th1细胞是CD的免疫特征之一。在258名荷兰CD患者和237名种族匹配的健康对照中研究了IL12B的3'UTR中的TaqI基因多态性和IRF1的3'UTR中的HinfI基因多态性的频率。在123个至少有一个患病儿童的家庭中确定了多态性变体从父母到患病儿童的传递情况。患者和对照之间IL12B TaqI基因多态性和IRF1 HinfI基因多态性的频率没有显著差异。此外，在家庭研究中，未发现任何多态性变体从父母到患病儿童的传递与预期有偏差。IL12B TaqI和IRF1 HinfI基因多态性似乎不参与CD的易感性。需要对驱动CD中Th1免疫病理学的因素进行进一步研究。
