The downstream modulator of interferon-γ, STAT1 is not genetically associated to the Dutch coeliac disease population

Abstract

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.

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma

“…STAT gene is a positional candidate located on chromosome 2 17. STAT gene may be associated with predisposition to allergic diseases 18.…”

The effect of gluten-free diet on Th1–Th2–Th3-associated intestinal immune responses in celiac disease

“…The janus kinase -signal transducer and activator of transcription (JAK-STAT) pathway, which mediates a Th1 (IFN-γ) response through activation of STAT proteins, has been reported to be of importance in the CD pathogenesis [7,9]. Apart from IFN-γ, also other cytokines as IFN-α/β, interleukin (IL) 6, TNF-α and transforming growth factor (TGF)- that can activate or cross-talk with the JAK-STAT signalling pathway are suggested to be of importance in CD [10,11].…”

Association of Genetic Polymorphisms in <i>STAT1</i> Gene with Increased Risk of Hepatocellular Carcinoma

“…Although polymorphisms in the STAT1 gene have been extensively studied in relation to other chronic diseases [20,21,22,23,24,25,26,27], few previous studies have been conducted in cancers. The only data are from two recent reports, one on sporadic medullary thyroid carcinoma [28], and the other on adult glioma [29].…”

“…These SNPs were selected based on: (i) previously published associations with various diseases [20,21,22,23,28], thus increasing the chance of selecting SNPs with functional consequences; (ii) minor allele frequency (MAF) of ≥0.05 in a Chinese population according to the databases of the International HapMap Project (http://www.hapmap.org/) and dbSNP of the National Center for Biotechnology Information, and (iii) SNP density of ≥1/10 kb.…”

“…A number of association studies of single nucleotide polymorphisms (SNPs) in the STAT1 gene with a risk of human diseases have focused on allergic, infectious and autoimmune disorders [20,21,22,23,24,25,26,27]. Despite the important role of STAT1 in carcinogenesis, there are only a few studies that have investigated STAT1 polymorphisms in relation to cancers [28,29].…”