A Polymorphism Affecting MYB Binding within the Promoter of the PDCD4 Gene is Associated with Severe Asthma in Children
Open accessAbstract
A previous genome-wide association study in asthma revealed putative associations that merit further investigation. In this study, the genome-wide significant associations of SNPs at the 5% false discovery rate were examined in independent groups of severe asthmatics. The panel consisted of 397 severe asthmatic adults, 116 severe asthmatic children, and a collection of 207 family-trios with an asthmatic proband. Three SNPs in the PDCD4 gene (rs6585018:G>A, rs1322997:C>A, and rs34104444:G>A) were significantly associated with severe childhood asthma (P values: 0.003, 0.002, 0.004) and total immunoglobulin E (IgE) levels (P values: 0.034, 0.041, 0.052). In an independent group of 234 asthmatic children and 652 controls, PDCD4 SNPs rs1407696:T>G and rs11195360:T>C were associated with total IgE levels (P values: 0.006, 0.014). 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. SNPs within MYB itself confer susceptibility to eosinophilia and asthma. 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.
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PDCD4 is an important factor for inflammatory diseases such as asthma and atherosclerosis.
“Recently, it was shown that PDCD4 is also an important factor for inflammatory diseases such as asthma [86] and atherosclerosis [87,88].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [86]
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- Authors
- Binia, A., Van Stiphout, N., Liang, L., Michel, S., Bhavsar, P. K., Fan Chung, K., Brightling, C. E., Barnes, P. J., Kabesch, M., Bush, A., Cookson, W. O. C., & Moffatt, M. F.
- Affiliations
- Nestlé (Switzerland) (CH)
- Department of Paediatric Respiratory Medicine National Heart and Lung Institute Imperial College London London United Kingdom
- Harvard University (US)
- University Hospital Regensburg (DE)
- Imperial College London (GB)
- Airway Disease Section, National Heart and Lung Institute Imperial College London London United Kingdom
- Institute for Lung Health Department of Infection Immunity and Inflammation University Hospitals of Leicester Leicester United Kingdom
- Corresponding author
- Binia, Aristea
- ORCID
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2013-05-20
- Volume
- 34
- Issue
- 8
- Pages
- 1131-1139
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- PMC
- PMC4296222
- OpenAlex
- W1999991110
- Cited by
- 24
- References
- 59
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Human Mutation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (097117, WT077959/Z/05/Z, 096964/Z/11/Z)
- National Institute for Health and Care Research (NF-SI-0510-10192)
- European Commission (018996)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PDCD4, promoter polymorphism, single nucleotide polymorphisms, total IgE, MYB binding site, gene expression regulation, asthma susceptibility, eosinophilia
- MeSH terms
- Adult, Asthma, Binding Sites, Cell Line, Child, Female, Haplotypes, Humans, Immunoglobulin E, Male, Promoter Regions, Genetic, Case-Control Studies, RNA-Binding Proteins, Proto-Oncogene Proteins c-myb, Polymorphism, Single Nucleotide, Apoptosis Regulatory Proteins, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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