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TRPA1 gene polymorphisms and childhood asthma

TRPA1 gene polymorphisms and childhood asthma
TRPA1 gene polymorphisms and childhood asthma
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.
0905-6157
1-27
Gallo, Valentina
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Dijk, F. Nicole
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Holloway, John W.
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Ring, Susan M.
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Koppelman, Gerard H.
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Postma, Dirkje S.
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Strachan, David P.
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Granell, Raquel
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de Jongste, Johan C.
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Jaddoe, Vincent W.V.
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den Dekker, Herman T.
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Duijts, Liesbeth
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Henderson, A. John
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Shaheen, Seif O.
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Gallo, Valentina
a60f6400-d194-441d-8d96-a201e46c60af
Dijk, F. Nicole
6be0d612-2be8-422a-8add-e6ff2ed5d2a8
Holloway, John W.
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Ring, Susan M.
55bebe97-d035-43f3-84a6-b57c5ea4c6be
Koppelman, Gerard H.
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Postma, Dirkje S.
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Strachan, David P.
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Granell, Raquel
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de Jongste, Johan C.
3902188e-c058-4f21-a024-148fa9c3c346
Jaddoe, Vincent W.V.
aa9c550e-f612-47d9-b12f-a8f409390a7d
den Dekker, Herman T.
c1065246-99c7-480b-9b7b-fcafb2c96ccc
Duijts, Liesbeth
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Henderson, A. John
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Shaheen, Seif O.
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Gallo, Valentina, Dijk, F. Nicole, Holloway, John W., Ring, Susan M., Koppelman, Gerard H., Postma, Dirkje S., Strachan, David P., Granell, Raquel, de Jongste, Johan C., Jaddoe, Vincent W.V., den Dekker, Herman T., Duijts, Liesbeth, Henderson, A. John and Shaheen, Seif O. (2016) TRPA1 gene polymorphisms and childhood asthma. Pediatric Allergy and Immunology, 1-27. (doi:10.1111/pai.12673).

Record type: Article

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.

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TRPA1 gene polymorphisms and childhood asthma _ Gallo V_FINAL.pdf - Accepted Manuscript
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Accepted/In Press date: 22 October 2016
e-pub ahead of print date: 25 October 2016
Organisations: Human Development & Health

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Local EPrints ID: 402056
URI: http://eprints.soton.ac.uk/id/eprint/402056
ISSN: 0905-6157
PURE UUID: 05275b1c-13aa-4363-9beb-7b35b3e121e1
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 26 Oct 2016 14:59
Last modified: 18 Feb 2021 16:49

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Contributors

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

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