TRPA1 Gene Polymorphisms and Childhood Asthma

Overview

Journal Pediatr Allergy Immunol

Specialty Pediatrics

Date 2016 Oct 26

PMID 27779810

Citations 29

Authors

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 John Henderson

Seif O Shaheen

Affiliations

Soon will be listed here.

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).

Citing Articles

Transient Receptor Potential Ankyrin 1 (TRPA1) Mediated LPS-Induced Inflammation in Periodontal Ligament Stem Cells by Inhibiting the Phosphorylation of JNK.

Wang X, Chen X, Gao J, Jin Z Stem Cells Int. 2024; 2024:7461604.

PMID: 39735214 PMC: 11679270. DOI: 10.1155/sci/7461604.

Ion Channels in the Immune Response of Asthma.

Yan L, Zhang L, Ogunniyi K, Hong L J Respir Biol Transl Med. 2024; 1(4).

PMID: 39664985 PMC: 11633837. DOI: 10.70322/jrbtm.2024.10019.

Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology.

Vlachova V, Barvik I, Zimova L Subcell Biochem. 2024; 104:207-244.

PMID: 38963489 DOI: 10.1007/978-3-031-58843-3_10.

A review of the pathophysiology and the role of ion channels on bronchial asthma.

Figueiredo I, Ferreira S, Fernandes J, Silva B, Vasconcelos L, Cavalcante F Front Pharmacol. 2023; 14:1236550.

PMID: 37841931 PMC: 10568497. DOI: 10.3389/fphar.2023.1236550.

Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study.

Robinson A, Huff R, Ryu M, Carlsten C Respir Res. 2023; 24(1):218.

PMID: 37679687 PMC: 10485933. DOI: 10.1186/s12931-023-02518-y.

References

Bessac B, Sivula M, von Hehn C, Escalera J, Cohn L, Jordt S . TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008; 118(5):1899-910. PMC: 2289796. DOI: 10.1172/JCI34192. View

Andre E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D . Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest. 2008; 118(7):2574-82. PMC: 2430498. DOI: 10.1172/JCI34886. View

Barnes P . Reactive oxygen species and airway inflammation. Free Radic Biol Med. 1990; 9(3):235-43. DOI: 10.1016/0891-5849(90)90034-g. View

Belvisi M, Dubuis E, Birrell M . Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest. 2011; 140(4):1040-1047. PMC: 3186687. DOI: 10.1378/chest.10-3327. View

Doehring A, Kusener N, Fluhr K, Neddermeyer T, Schneider G, Lotsch J . Effect sizes in experimental pain produced by gender, genetic variants and sensitization procedures. PLoS One. 2011; 6(3):e17724. PMC: 3053372. DOI: 10.1371/journal.pone.0017724. View

Brunekreef B, Smit J, de Jongste J, Neijens H, Gerritsen J, Postma D . The prevention and incidence of asthma and mite allergy (PIAMA) birth cohort study: design and first results. Pediatr Allergy Immunol. 2003; 13(s15):55-60. DOI: 10.1034/j.1399-3038.13.s.15.1.x. View

Nassini R, Materazzi S, Andre E, Sartiani L, Aldini G, Trevisani M . Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents. FASEB J. 2010; 24(12):4904-16. DOI: 10.1096/fj.10-162438. View

Nyholt D . A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004; 74(4):765-9. PMC: 1181954. DOI: 10.1086/383251. View

Meyers D, Bleecker E, Holloway J, Holgate S . Asthma genetics and personalised medicine. Lancet Respir Med. 2014; 2(5):405-15. PMC: 4768462. DOI: 10.1016/S2213-2600(14)70012-8. View

10.

Barrett J, Fry B, Maller J, Daly M . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2004; 21(2):263-5. DOI: 10.1093/bioinformatics/bth457. View

11.

Bautista D, Pellegrino M, Tsunozaki M . TRPA1: A gatekeeper for inflammation. Annu Rev Physiol. 2012; 75:181-200. PMC: 4041114. DOI: 10.1146/annurev-physiol-030212-183811. View

12.

Smit L, Kogevinas M, Anto J, Bouzigon E, Gonzalez J, Le Moual N . Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respir Res. 2012; 13:26. PMC: 3342106. DOI: 10.1186/1465-9921-13-26. View

13.

Kruithof C, Kooijman M, Van Duijn C, Franco O, de Jongste J, Klaver C . The Generation R Study: Biobank update 2015. Eur J Epidemiol. 2014; 29(12):911-27. DOI: 10.1007/s10654-014-9980-6. View

14.

Shaheen S, Sterne J, Songhurst C, Burney P . Frequent paracetamol use and asthma in adults. Thorax. 2000; 55(4):266-70. PMC: 1745727. DOI: 10.1136/thorax.55.4.266. View

15.

Lotvall J, Akdis C, Bacharier L, Bjermer L, Casale T, Custovic A . Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011; 127(2):355-60. DOI: 10.1016/j.jaci.2010.11.037. View

16.

Henderson A, Shaheen S . Acetaminophen and asthma. Paediatr Respir Rev. 2013; 14(1):9-15. DOI: 10.1016/j.prrv.2012.04.004. View

17.

Gallo V, Dijk F, Holloway J, Ring S, Koppelman G, Postma D . TRPA1 gene polymorphisms and childhood asthma. Pediatr Allergy Immunol. 2016; 28(2):191-198. PMC: 5324656. DOI: 10.1111/pai.12673. View

18.

Bonnelykke K, Sleiman P, Nielsen K, Kreiner-Moller E, Mercader J, Belgrave D . A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2013; 46(1):51-5. DOI: 10.1038/ng.2830. View

19.

Nassini R, Pedretti P, Moretto N, Fusi C, Carnini C, Facchinetti F . Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One. 2012; 7(8):e42454. PMC: 3419223. DOI: 10.1371/journal.pone.0042454. View

20.

Jaddoe V, van Duijn C, van der Heijden A, Mackenbach J, Moll H, Steegers E . The Generation R Study: design and cohort update 2010. Eur J Epidemiol. 2010; 25(11):823-41. PMC: 2991548. DOI: 10.1007/s10654-010-9516-7. View