Limits...
A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is associated with severe asthma in children.

Binia A, Van Stiphout N, Liang L, Michel S, Bhavsar PK, Fan Chung K, Brightling CE, Barnes PJ, Kabesch M, Bush A, Cookson WO, Moffatt MF - Hum. Mutat. (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. aristea.binia@rdls.nestle.com

Show MeSH

Related in: MedlinePlus

The outline of the study plan (N: number; FDR: false discovery rate; B58C: British 1958 Birth Cohort study).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4296222&req=5

fig01: The outline of the study plan (N: number; FDR: false discovery rate; B58C: British 1958 Birth Cohort study).

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).


A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is associated with severe asthma in children.

Binia A, Van Stiphout N, Liang L, Michel S, Bhavsar PK, Fan Chung K, Brightling CE, Barnes PJ, Kabesch M, Bush A, Cookson WO, Moffatt MF - Hum. Mutat. (2013)

The outline of the study plan (N: number; FDR: false discovery rate; B58C: British 1958 Birth Cohort study).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296222&req=5

fig01: The outline of the study plan (N: number; FDR: false discovery rate; B58C: British 1958 Birth Cohort study).
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. aristea.binia@rdls.nestle.com

Show MeSH
Related in: MedlinePlus