The University of Southampton
University of Southampton Institutional Repository

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: a birth cohort study

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: a birth cohort study
Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: a birth cohort study

Background: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking.

Objective: this study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy.

Methods: infants enrolled in a birth cohort study (n = 94) were assessed for eczema at ages 3-, 6-, and 12-months. Five probes measuring FLG transcripts expression in UCB were available from genome-wide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression.

Results: increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR = 0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR = 2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3-months of age was high (AUC: 0.91, 95% CI: 0.84-0.98).

Conclusions and clinical relevance: this study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention. This article is protected by copyright. All rights reserved.

Journal Article
0954-7894
1185-1192
Ziyab, Ali H
12905e44-3fd1-47c2-98e5-35320e89815b
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Lockett, Gabrielle A
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ziyab, Ali H
12905e44-3fd1-47c2-98e5-35320e89815b
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Lockett, Gabrielle A
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Ziyab, Ali H, Ewart, Susan, Lockett, Gabrielle A, Zhang, Hongmei, Arshad, Syed, Holloway, John W and Karmaus, Wilfried (2017) Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: a birth cohort study. Clinical & Experimental Allergy, 47 (9), 1185-1192. (doi:10.1111/cea.12956).

Record type: Article

Abstract

Background: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking.

Objective: this study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy.

Methods: infants enrolled in a birth cohort study (n = 94) were assessed for eczema at ages 3-, 6-, and 12-months. Five probes measuring FLG transcripts expression in UCB were available from genome-wide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression.

Results: increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR = 0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR = 2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3-months of age was high (AUC: 0.91, 95% CI: 0.84-0.98).

Conclusions and clinical relevance: this study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention. This article is protected by copyright. All rights reserved.

Text
FLG_expression_eczema_4_17_2017_UnMarked - Accepted Manuscript
Download (115kB)

More information

Accepted/In Press date: 5 May 2017
e-pub ahead of print date: 14 May 2017
Published date: 1 September 2017
Additional Information: This article is protected by copyright. All rights reserved.
Keywords: Journal Article
Organisations: Epigenetics, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 410460
URI: https://eprints.soton.ac.uk/id/eprint/410460
ISSN: 0954-7894
PURE UUID: 3d40d714-31d9-4cfa-9929-82335088367f
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 08 Jun 2017 16:31
Last modified: 10 Dec 2019 06:01

Export record

Altmetrics

Contributors

Author: Ali H Ziyab
Author: Susan Ewart
Author: Gabrielle A Lockett
Author: Hongmei Zhang
Author: Syed Arshad
Author: John W Holloway ORCID iD
Author: Wilfried Karmaus

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×