PMID- 24568840
OWN - NLM
STAT- MEDLINE
DCOM- 20141204
LR  - 20220129
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 134
IP  - 1
DP  - 2014 Jul
TI  - Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with 
      wheezing phenotypes and asthma in childhood.
PG  - 170-7
LID - S0091-6749(14)00059-1 [pii]
LID - 10.1016/j.jaci.2013.12.1080 [doi]
AB  - BACKGROUND: Genome-wide association studies identified IL33 and IL-1 
      receptor-like 1 (IL1RL1)/IL18R1 as asthma susceptibility loci. IL33 and IL1RL1 
      constitute a single ligand-receptor pathway. OBJECTIVE: In 2 birth cohorts, the 
      Prevalence and Incidence of Asthma and Mite Allergy (PIAMA) study and Avon 
      Longitudinal Study of Parents and Children (ALSPAC), we analyzed associations of 
      longitudinal wheezing phenotypes and asthma with single nucleotide polymorphisms 
      (SNPs) of 8 genes encoding IL-33, IL1RL1, its coreceptor IL1RAcP, its adaptors 
      myeloid differentiation primary response gene 88 (MyD88) and Toll-IL-11 receptor 
      domain containing adaptor protein (TIRAP), and the downstream IL-1 
      receptor-associated kinase 1, IL-1 receptor-associated kinase 4, and TNF 
      receptor-associated factor 6 (TRAF6). Furthermore, we investigated whether SNPs 
      in this pathway show replicable evidence of gene-gene interaction. METHODS: 
      Ninety-four SNPs were investigated in 2007 children in the PIAMA study and 7247 
      children in ALSPAC. Associations with wheezing phenotypes and asthma at 8 years 
      of age were analyzed in each cohort and subsequently meta-analyzed. Gene-gene 
      interactions were assessed through model-based multifactor dimensionality 
      reduction in the PIAMA study, and gene-gene interactions of 10 SNP pairs were 
      further evaluated. RESULTS: Intermediate-onset wheeze was associated with SNPs in 
      several genes in the IL33-IL1RL1 pathway after applying multiple testing 
      correction in the meta-analysis: 2 IL33 SNPs (rs4742170 and rs7037276), 1 IL-1 
      receptor accessory protein (IL1RAP) SNP (rs10513854), and 1 TRAF6 SNP 
      (rs5030411). Late-onset wheeze was associated with 2 IL1RL1 SNPs (rs10208293 and 
      rs13424006), and persistent wheeze was associated with 1 IL33 SNP (rs1342326) and 
      1 IL1RAP SNP (rs9290936). IL33 and IL1RL1 SNPs were nominally associated with 
      asthma. Three SNP pairs showed interaction for asthma in the PIAMA study but not 
      in ALSPAC. CONCLUSIONS: IL33-IL1RL1 pathway polymorphisms are associated with 
      asthma and specific wheezing phenotypes; that is, most SNPs are associated with 
      intermediate-onset wheeze, a phenotype closely associated with sensitization. We 
      speculate that IL33-IL1RL1 pathway polymorphisms affect development of wheeze and 
      subsequent asthma through sensitization in early childhood.
CI  - Copyright (c) 2014 American Academy of Allergy, Asthma & Immunology. Published by 
      Mosby, Inc. All rights reserved.
FAU - Savenije, Olga E
AU  - Savenije OE
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Epidemiology, GRIAC Research Institute, Groningen, The Netherlands; University of 
      Groningen, University Medical Center Groningen, Department of Pediatrics, Beatrix 
      Children's Hospital, GRIAC Research Institute, Groningen, The Netherlands.
FAU - Mahachie John, Jestinah M
AU  - Mahachie John JM
AD  - Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, 
      Belgium; Bioinformatics and Modeling, GIGA-R, University of Liege, Liege, 
      Belgium.
FAU - Granell, Raquel
AU  - Granell R
AD  - School of Social and Community Medicine, University of Bristol, Bristol, United 
      Kingdom.
FAU - Kerkhof, Marjan
AU  - Kerkhof M
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Epidemiology, GRIAC Research Institute, Groningen, The Netherlands.
FAU - Dijk, F Nicole
AU  - Dijk FN
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, 
      GRIAC Research Institute, Groningen, The Netherlands.
FAU - de Jongste, Johan C
AU  - de Jongste JC
AD  - Department of Pediatrics/Respiratory Medicine, Erasmus University Medical 
      Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
FAU - Smit, Henriette A
AU  - Smit HA
AD  - Julius Center for Health Sciences and Primary Care, University Medical Center 
      Utrecht, Utrecht, The Netherlands.
FAU - Brunekreef, Bert
AU  - Brunekreef B
AD  - Julius Center for Health Sciences and Primary Care, University Medical Center 
      Utrecht, Utrecht, The Netherlands; Institute for Risk Assessment Sciences, 
      Utrecht University, Utrecht, The Netherlands.
FAU - Postma, Dirkje S
AU  - Postma DS
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Pulmonology, GRIAC Research Institute, Groningen, The Netherlands.
FAU - Van Steen, Kristel
AU  - Van Steen K
AD  - Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, 
      Belgium; Bioinformatics and Modeling, GIGA-R, University of Liege, Liege, 
      Belgium.
FAU - Henderson, John
AU  - Henderson J
AD  - School of Social and Community Medicine, University of Bristol, Bristol, United 
      Kingdom.
FAU - Koppelman, Gerard H
AU  - Koppelman GH
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, 
      GRIAC Research Institute, Groningen, The Netherlands. Electronic address: 
      g.h.koppelman@umcg.nl.
LA  - eng
GR  - 092731/Wellcome Trust/United Kingdom
GR  - 102215/Wellcome Trust/United Kingdom
GR  - G9815508/MRC_/Medical Research Council/United Kingdom
GR  - MC_PC_15018/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140222
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (IL1RAP protein, human)
RN  - 0 (IL1RL1 protein, human)
RN  - 0 (IL33 protein, human)
RN  - 0 (Interleukin-1 Receptor Accessory Protein)
RN  - 0 (Interleukin-1 Receptor-Like 1 Protein)
RN  - 0 (Interleukin-33)
RN  - 0 (Interleukins)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (TIRAP protein, human)
SB  - IM
MH  - Asthma/*genetics/immunology/pathology
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Epistasis, Genetic
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Interleukin-1 Receptor Accessory Protein/genetics/immunology
MH  - Interleukin-1 Receptor-Like 1 Protein
MH  - Interleukin-33
MH  - Interleukins/*genetics/immunology
MH  - Male
MH  - Membrane Glycoproteins/genetics/immunology
MH  - Myeloid Differentiation Factor 88/genetics/immunology
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Cell Surface/*genetics/immunology
MH  - Receptors, Interleukin-1/genetics/immunology
MH  - Respiratory Sounds/immunology/*physiopathology
MH  - Signal Transduction
OTO - NOTNLM
OT  - Avon Longitudinal Study of Parents and Children study
OT  - IL1RL1
OT  - IL33
OT  - IL33-IL1RL1 pathway
OT  - Prevalence and Incidence of Asthma and Mite Allergy study
OT  - asthma
OT  - children
OT  - wheezing phenotypes
EDAT- 2014/02/27 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/27 06:00
PHST- 2013/06/02 00:00 [received]
PHST- 2013/11/20 00:00 [revised]
PHST- 2013/12/17 00:00 [accepted]
PHST- 2014/02/27 06:00 [entrez]
PHST- 2014/02/27 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0091-6749(14)00059-1 [pii]
AID - 10.1016/j.jaci.2013.12.1080 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2014 Jul;134(1):170-7. doi: 10.1016/j.jaci.2013.12.1080. 
      Epub 2014 Feb 22.