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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.European Journal of Human Genetics (2006) 14, 1120–1124. doi:10.1038/sj.ejhg.5201667; published online 14 June 2006 [ABSTRACT FROM AUTHOR]

An increasing number of findings from epidemiological studies support associations between exposure to air pollution and the onset of several diseases, including pulmonary, cardiovascular and neurodegenerative diseases, and malignancies. However, intermediate, and potentially mediating, biological mechanisms associated with exposure to air pollutants are largely unknown. Previous studies on the human exposome have shown that the expression of certain circulating microRNAs (miRNAs), regulators of gene expression, are altered upon exposure to traffic-related air pollutants. In the present study, we investigated the relationship between particulate matter (PM) smaller than 2.5 μm (PM 2.5), PM 2.5 absorbance (as a proxy of black carbon and soot), and ultrafine-particles (UFP, smaller than 0.1 μm), measured in healthy volunteers by 24 h personal monitoring (PEM) sessions and global expression levels of peripheral blood miRNAs. The PEM sessions were conducted in four European countries, namely Switzerland (Basel), United Kingdom (Norwich), Italy (Turin), and The Netherlands (Utrecht). miRNAs expression levels were analysed using microarray technology on blood samples from 143 participants. Seven miRNAs, hsa-miR-24-3p, hsa-miR-4454, hsa-miR-4763-3p, hsa-miR-425-5p, hsa-let-7d-5p, hsa-miR-502-5p, and hsa-miR-505-3p were significantly (FDR corrected) expressed in association with PM 2.5 personal exposure, while no significant association was found between miRNA expression and the other pollutants. The results obtained from this investigation suggest that personal exposure to PM 2.5 is associated with miRNA expression levels, showing the potential for these circulating miRNAs as novel biomarkers for air pollution health risk assessment. Image 1 • Seven miRNAs measured in peripheral blood were significantly (FDR corrected) expressed in association with personal exposure to PM 2.5. • 368 target genes were identified for the seven miRNAs associated with PM 2.5 personal exposure levels and p53 signaling pathways, pathways in cancer, and JAK-STAT signaling pathway were identified as significantly enriched. • The results from this study suggest that miRNA expression levels are be related to exposure. [ABSTRACT FROM AUTHOR]