Garrote José A, Arranz Eduardo, Tellería Juan J, Castro Jesús, Calvo Carmen, Blanco-Quirós Alfredo
Laboratorio de Pediatría, Area de Pediatría e Inmunología-IBGM, Universidad de Valladolid, Facultad de Medicina, C/ Ramón y Cajal 7, 47005 Valladolid, Spain.
Immunogenetics. 2002 Nov;54(8):551-5. doi: 10.1007/s00251-002-0498-9. Epub 2002 Oct 3.
TNFalpha and TNFbeta, or linfotoxin (LTalpha), are two molecules playing an important role in inflammation. Their genes map on Chromosome 6, between the HLA class II and class I loci. Polymorphisms in, or near, TNF genes have been associated with susceptibility to several autoimmune diseases. Studies of TNF genes in celiac disease (CD) have presented contradictory results. We have assessed the role of TNFalpha and linfotoxin alpha (TNFbeta) in CD and their relative value as CD markers in addition to the presence of DQ2. The TNFA -308 polymorphism and the polymorphism at the first intron of the LTA gene were typed in CD patients and healthy controls and the results were correlated with the presence of DQ2. Significant differences were found in genotype and allele frequencies for the TNFA and LTA genes between CD patients and controls, with an increase in the presence of the TNFA2 and LTA1 alleles in CD patients. These differences increase when DQ2-positive CD patients and DQ2-positive controls are compared. In DQ2-positive individuals, allele 2 (A) in position -308 of the promoter of TNFA and allele 1 (G) of the NcoI RFLP in the first intron of LTA are additional risk markers for CD.
肿瘤坏死因子α（TNFα）和肿瘤坏死因子β，即淋巴毒素（LTα），是在炎症中发挥重要作用的两种分子。它们的基因定位于6号染色体上，在HLAⅡ类和Ⅰ类基因座之间。TNF基因内部或附近的多态性与多种自身免疫性疾病的易感性相关。对乳糜泻（CD）患者TNF基因的研究结果相互矛盾。我们评估了TNFα和淋巴毒素α（TNFβ）在CD中的作用，以及它们作为除DQ2之外的CD标志物的相对价值。对CD患者和健康对照者进行了TNFA -308多态性和LTA基因第一内含子多态性分型，并将结果与DQ2的存在情况进行关联分析。结果发现，CD患者与对照者在TNFA和LTA基因的基因型和等位基因频率上存在显著差异，CD患者中TNFA2和LTA1等位基因的出现频率增加。当比较DQ2阳性的CD患者和DQ2阳性对照者时，这些差异更加明显。在DQ2阳性个体中，TNFA启动子-308位的2号等位基因（A）和LTA第一内含子NcoI RFLP的1号等位基因（G）是CD的额外风险标志物。
