PMID- 23606399
OWN - NLM
STAT- MEDLINE
DCOM- 20140122
LR  - 20231104
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 34
IP  - 8
DP  - 2013 Aug
TI  - A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is 
      associated with severe asthma in children.
PG  - 1131-9
LID - 10.1002/humu.22340 [doi]
AB  - 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.
CI  - (c) 2013 WILEY PERIODICALS, INC.
FAU - Binia, Aristea
AU  - Binia A
AD  - Molecular Genetics and Genomics Section, National Heart and Lung Institute, 
      Imperial College London, London, United Kingdom. aristea.binia@rdls.nestle.com
FAU - Van Stiphout, Nicole
AU  - Van Stiphout N
FAU - Liang, Liming
AU  - Liang L
FAU - Michel, Sven
AU  - Michel S
FAU - Bhavsar, Pankaj K
AU  - Bhavsar PK
FAU - Fan Chung, K
AU  - Fan Chung K
FAU - Brightling, Chris E
AU  - Brightling CE
FAU - Barnes, Peter J
AU  - Barnes PJ
FAU - Kabesch, Michael
AU  - Kabesch M
FAU - Bush, Andrew
AU  - Bush A
FAU - Cookson, William O C
AU  - Cookson WO
FAU - Moffatt, Miriam F
AU  - Moffatt MF
LA  - eng
GR  - 097117/WT_/Wellcome Trust/United Kingdom
GR  - WT077959/Z/05/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130520
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (PDCD4 protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myb)
RN  - 0 (RNA-Binding Proteins)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adult
MH  - Apoptosis Regulatory Proteins/*genetics/metabolism
MH  - Asthma/*genetics
MH  - Binding Sites
MH  - Case-Control Studies
MH  - Cell Line
MH  - Child
MH  - Female
MH  - Genome-Wide Association Study
MH  - Haplotypes
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Male
MH  - *Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-myb/*genetics/metabolism
MH  - RNA-Binding Proteins/*genetics/metabolism
PMC - PMC4296222
OTO - NOTNLM
OT  - MYB
OT  - PDCD4
OT  - asthma
OT  - childhood
OT  - severe
EDAT- 2013/04/23 06:00
MHDA- 2014/01/23 06:00
CRDT- 2013/04/23 06:00
PHST- 2012/11/01 00:00 [received]
PHST- 2013/04/12 00:00 [accepted]
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2014/01/23 06:00 [medline]
AID - 10.1002/humu.22340 [doi]
PST - ppublish
SO  - Hum Mutat. 2013 Aug;34(8):1131-9. doi: 10.1002/humu.22340. Epub 2013 May 20.