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

doi:10.1111/pai.12673

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 journal › Article (Academic Journal) › peer-review

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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 language	English
Pages (from-to)	191-198
Number of pages	8
Journal	Pediatric Allergy and Immunology
Volume	28
Issue number	2
Early online date	8 Dec 2016
DOIs	https://doi.org/10.1111/pai.12673
Publication status	Published - 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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@article{2f80cd1cce904f5e9976d22cd26ad79a,

title = "TRPA1 gene polymorphisms and childhood asthma",

abstract = "BackgroundAnimal 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.MethodsWe 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.ResultsIn 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.ConclusionThis study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words)",

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",

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

year = "2017",

month = mar,

doi = "10.1111/pai.12673",

language = "English",

volume = "28",

pages = "191--198",

journal = "Pediatric Allergy and Immunology",

issn = "0905-6157",

publisher = "Munksgaard International Publishers",

number = "2",

}

TY - JOUR

T1 - TRPA1 gene polymorphisms and childhood asthma

AU - Gallo, Valentina

AU - Dijk, F. Nicole

AU - Holloway, John W

AU - Ring, Susan M.

AU - Koppelman, Gerard H.

AU - Postma, Dirkje S.

AU - Strachan, David P.

AU - Granell, Raquel

AU - de Jongste, Johan C.

AU - Jaddoe, Vincent W.V.

AU - den Dekker, Herman T.

AU - Duijts, Liesbeth

AU - Henderson, A J W

AU - Shaheen, Seif O.

PY - 2017/3

Y1 - 2017/3

N2 - BackgroundAnimal 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.MethodsWe 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.ResultsIn 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.ConclusionThis study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words)

AB - BackgroundAnimal 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.MethodsWe 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.ResultsIn 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.ConclusionThis study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words)

KW - Avon Longitudinal Study of Parents and Children

KW - asthma

KW - birth cohort

KW - Generation R

KW - gene–environment interaction

KW - genotype

KW - paracetamol

KW - Prevention and Incidence of Asthma and Mite Allergy

KW - prenatal exposure

KW - transient receptor potential ankyrin-1

UR - http://www.scopus.com/inward/record.url?scp=85006482447&partnerID=8YFLogxK

U2 - 10.1111/pai.12673

DO - 10.1111/pai.12673

M3 - Article (Academic Journal)

C2 - 27779810

AN - SCOPUS:85006482447

SN - 0905-6157

VL - 28

SP - 191

EP - 198

JO - Pediatric Allergy and Immunology

JF - Pediatric Allergy and Immunology

IS - 2

ER -

TRPA1 gene polymorphisms and childhood asthma

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THE NATURAL HISTORY OF ASTHMA AND WHEEZING ILLNESSES FROM BIRTH TO ADOLESCENCE: DETERMINANTS OF THE REMISSION OF ASTHMA

EXTENSION OF RD1321 VIA IOP.

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TRPA1 gene polymorphisms and childhood asthma

Abstract

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THE NATURAL HISTORY OF ASTHMA AND WHEEZING ILLNESSES FROM BIRTH TO ADOLESCENCE: DETERMINANTS OF THE REMISSION OF ASTHMA

EXTENSION OF RD1321 VIA IOP.

Cite this