Diosdado Begoña, Monsuur Alienke J, Mearin María Luisa, Mulder Chris, Wijmenga Cisca
Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
Eur J Hum Genet. 2006 Oct;14(10):1120-4. doi: 10.1038/sj.ejhg.5201667. Epub 2006 Jun 14.
Coeliac disease (CD) is a complex genetic disorder. Its etiology is owing to multiple genes and environmental factors, such as gluten. The first event in the pathogenesis of CD after the ingestion of gluten is the activation of a Th1 immune response that leads to villous atrophy. Although this immune response seems crucial to the disease's development, only the HLA-DQ2/DQ8 genes have been identified as causative immune genes related to CD. Recently, the activation of the transcription factor STAT1 and changes in its expression levels have confirmed the participation of the Janus kinase-signal transducer and activator of transcription pathway in CD. Furthermore, as the STAT-1 gene is a positional candidate located in the CELIAC3 locus on chromosome 2, we speculate that alterations in this gene could be primarily responsible for the aberrant immune response that characterizes CD. Based on this functional and genetic evidence, we investigated the primary contribution of STAT-1 to CD. We performed a comprehensive genetic association study using five tag SNPs fully covering the STAT-1 gene in a Dutch cohort of 355 independent CD cases and 360 healthy controls. Neither the alleles, nor the genotypes in the case-control genetic association studies, nor the haplotype analysis showed any association to the STAT-1 gene in the Dutch CD population. Our results do not point to a primary involvement of the STAT-1 gene in the Dutch CD population.
乳糜泻（CD）是一种复杂的遗传性疾病。其病因归因于多个基因和环境因素，如麸质。摄入麸质后，CD发病机制中的首个事件是Th1免疫反应的激活，这会导致绒毛萎缩。尽管这种免疫反应似乎对疾病发展至关重要，但仅HLA - DQ2/DQ8基因被确定为与CD相关的致病性免疫基因。最近，转录因子STAT1的激活及其表达水平的变化证实了Janus激酶 - 信号转导子和转录激活子途径参与了CD。此外，由于STAT - 1基因是位于2号染色体CELIAC3位点的位置候选基因，我们推测该基因的改变可能是导致CD特征性异常免疫反应的主要原因。基于这些功能和遗传证据，我们研究了STAT - 1对CD的主要作用。我们在一个由355例独立CD病例和360例健康对照组成的荷兰队列中，使用五个完全覆盖STAT - 1基因的标签单核苷酸多态性（tag SNPs）进行了全面的基因关联研究。在病例对照基因关联研究中，等位基因、基因型以及单倍型分析均未显示与荷兰CD人群中的STAT - 1基因存在任何关联。我们的结果并不表明STAT - 1基因在荷兰CD人群中起主要作用。
