Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2017 Mar;28(2):191-198.
doi: 10.1111/pai.12673. Epub 2016 Dec 8.

TRPA1 gene polymorphisms and childhood asthma

Valentina Gallo  1 , F Nicole Dijk  2 , John W Holloway  3 , Susan M Ring  4   5 , Gerard H Koppelman  2 , Dirkje S Postma  6 , David P Strachan  7 , Raquel Granell  4 , Johan C de Jongste  8 , Vincent W V Jaddoe  9   10   11 , Herman T den Dekker  8   9   10 , Liesbeth Duijts  8   10   12 , A John Henderson  4 , Seif O Shaheen  1
Affiliations
Multicenter Study

TRPA1 gene polymorphisms and childhood asthma

Valentina Gallo et al. Pediatr Allergy Immunol. 2017 Mar.

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).

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Forest plots showing meta‐analysis of the per‐allele associations between the six TRPA1 SNPs most significantly associated with asthma in ALSPAC and current asthma in ALSPAC, PIAMA and Generation R.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kang K, Pulver SR, Panzano VC, et al. Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature 2010: 464: 597–600. - PMC - PubMed
    1. Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Investig 2008: 118: 1899–910. - PMC - PubMed
    1. Facchinetti FP, Patacchini R. The rising role of TRPA1 in asthma. Open Drug Discov J. 2010: 2: 71–80.
    1. Belvisi MG, Dubuis E, Birrell MA. Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest 2011: 140: 1040–7. - PMC - PubMed
    1. Bautista DM, Pellegrino M, Tsunozaki M. TRPA1: a gatekeeper for inflammation. Annu Rev Physiol 2013: 75: 181–200. - PMC - PubMed

Publication types