title: TRPA1 gene polymorphisms and childhood asthma.
abstract: Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes.
  
  
  
  We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure.
  
  
  
  In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 (OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 (OR 1.30 (1.09-1.55), p = 0.003), rs920829 (OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 (OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were.
  
  
  
  This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words).
authors: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, London, UK.
authors: Valentina
authors: V
authors: Gallo
authors: Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: F Nicole
authors: FN
authors: Dijk
authors: Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
authors: John W
authors: 0000-0001-9998-0464
authors: JW
authors: Holloway
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
authors: Susan M
authors: SM
authors: Ring
authors: Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Gerard H
authors: GH
authors: Koppelman
authors: Department of Pulmonology, Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Dirkje S
authors: DS
authors: Postma
authors: St George's, University of London, London, UK.
authors: David P
authors: DP
authors: Strachan
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors: Raquel
authors: R
authors: Granell
authors: Division of Respiratory Medicine, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Johan C
authors: JC
authors: de Jongste
authors: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Vincent W V
authors: VW
authors: Jaddoe
authors: Division of Respiratory Medicine, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Herman T
authors: HT
authors: den Dekker
authors: Division of Respiratory Medicine, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.|Division of Neonatology, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Liesbeth
authors: L
authors: Duijts
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors: A John
authors: AJ
authors: Henderson
authors: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, London, UK.
authors: Seif O
authors: SO
authors: Shaheen
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D018811:Maternal Exposure / Q000009:adverse effects; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D000074025:TRPA1 Cation Channel / Q000235:genetics*
chemical_list: D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D000082:Acetaminophen; D007073:Immunoglobulin E
keywords: Avon Longitudinal Study of Parents and Children; Generation R; Prevention and Incidence of Asthma and Mite Allergy; asthma; birth cohort; gene-environment interaction; genotype; paracetamol; prenatal exposure; transient receptor potential ankyrin-1