TRPA1 gene polymorphisms and childhood asthma

Valentina Gallo, F. Nicole Dijk, John W Holloway, Susan M. Ring, Gerard H. Koppelman, Dirkje S. Postma, David P. Strachan, Raquel Granell, Johan C. de Jongste, Vincent W.V. Jaddoe, Herman T. den Dekker, Liesbeth Duijts, A J W Henderson, Seif O. Shaheen*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
209 Downloads (Pure)

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words)
Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalPediatric Allergy and Immunology
Volume28
Issue number2
Early online date8 Dec 2016
DOIs
Publication statusPublished - Mar 2017

Keywords

  • Avon Longitudinal Study of Parents and Children
  • asthma
  • birth cohort
  • Generation R
  • gene–environment interaction
  • genotype
  • paracetamol
  • Prevention and Incidence of Asthma and Mite Allergy
  • prenatal exposure
  • transient receptor potential ankyrin-1

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