A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is associated with severe asthma in children.
Bottom Line: In silico analysis of PDCD4 locus showed that rs6585018:G>A had the potential to affect MYB transcription factor binding, shown to act as a PDCD4-transcription inducer.Electromobility shift assays and reporter assays revealed that rs6585018:G>A alters MYB binding thereby influencing the expression of PDCD4.Our association between a variant MYB binding site in PDCD4 and the severest form of childhood asthma therefore suggests that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses.
Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. firstname.lastname@example.orgShow MeSH
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Mentions: In addition to the 17q21 locus exceeding the genome-wide significance level (at 1% false discovery rate, FDR), genetic markers showed suggestive results at 5% FDR [Moffatt et al., 2007]. Evidently a great proportion of these represent false positive results [McCarthy et al., 2008]; however some of these hits could point to further asthma-associated loci with a smaller effect not captured by the GWAS. This study aimed to further investigate these underlying associations in cases of child and adult severe asthma followed by fine-mapping and functional assays (Fig. 1).
Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. email@example.com