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Association of Filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier?

Association of Filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier?
Association of Filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier?
Background: Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis.

Methods: In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrin haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions.

Results:FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, ‘FLG variants plus allergic sensitization' and ‘FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis.

Conclusions: Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different
1018-2438
308-318
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Steck, Susan E.
9c8c6733-ebfe-49e6-bb66-9d8df59d31e8
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Steck, Susan E.
9c8c6733-ebfe-49e6-bb66-9d8df59d31e8
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958

Ziyab, Ali H., Karmaus, Wilfried, Zhang, Hongmei, Holloway, John W., Steck, Susan E., Ewart, Susan and Arshad, Syed Hasan (2014) Association of Filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier? International Archives of Allergy and Immunology, 164 (4), 308-318. (doi:10.1159/000365990).

Record type: Article

Abstract

Background: Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis.

Methods: In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrin haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions.

Results:FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, ‘FLG variants plus allergic sensitization' and ‘FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis.

Conclusions: Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different

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More information

Published date: 23 September 2014
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 369893
URI: https://eprints.soton.ac.uk/id/eprint/369893
ISSN: 1018-2438
PURE UUID: 149f8bc3-3be6-42ba-8f4e-02fc0031d4ea
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 13 Oct 2014 13:50
Last modified: 06 Jun 2018 12:59

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