Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life

Anke Hüls; Claudia Klümper; Elaina A MacIntyre; Michael Brauer; Erik Melén; Mario Bauer; Dietrich Berdel; Anna Bergström; Bert Brunekreef; Moira Chan-Yeung; Elaine Fuertes; Ulrike Gehring; Anna Gref; Joachim Heinrich; Marie Standl; Irina Lehmann; Marjan Kerkhof; Gerard H Koppelman; Anita L Kozyrskyj; Göran Pershagen; Christopher Carlsten; Ursula Krämer; Tamara Schikowski; TAG Study Group

doi:10.1111/pai.12903

Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life

Anke Hüls, Claudia Klümper, Elaina A MacIntyre, Michael Brauer, Erik Melén, Mario Bauer, Dietrich Berdel, Anna Bergström, Bert Brunekreef, Moira Chan-Yeung, Elaine Fuertes, Ulrike Gehring, Anna Gref, Joachim Heinrich, Marie Standl, Irina Lehmann, Marjan Kerkhof, Gerard H Koppelman, Anita L Kozyrskyj, Göran PershagenChristopher Carlsten, Ursula Krämer, Tamara Schikowski, TAG Study Group

Chair Leseman

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation.

METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP.

RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population.

CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.

Original language	English
Pages (from-to)	596-605
Number of pages	10
Journal	Pediatric Allergy and Immunology
Volume	29
Issue number	6
DOIs	https://doi.org/10.1111/pai.12903
Publication status	Published - Sept 2018

Keywords

atopic eczema
gene-environment interaction
weighted genetic risk scores

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10.1111/pai.12903

hulsFinal published version, 551 KBLicence: Taverne

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Hüls, A., Klümper, C., MacIntyre, E. A., Brauer, M., Melén, E., Bauer, M., Berdel, D., Bergström, A., Brunekreef, B., Chan-Yeung, M., Fuertes, E., Gehring, U., Gref, A., Heinrich, J., Standl, M., Lehmann, I., Kerkhof, M., Koppelman, G. H., Kozyrskyj, A. L., ... TAG Study Group (2018). Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life. Pediatric Allergy and Immunology, 29(6), 596-605. https://doi.org/10.1111/pai.12903

@article{78eed43e1094497ba6b42fade2e686a2,

title = "Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life",

abstract = "BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation.METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP.RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population.CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.",

keywords = "atopic eczema, gene-environment interaction, weighted genetic risk scores",

author = "Anke H{\"u}ls and Claudia Kl{\"u}mper and MacIntyre, {Elaina A} and Michael Brauer and Erik Mel{\'e}n and Mario Bauer and Dietrich Berdel and Anna Bergstr{\"o}m and Bert Brunekreef and Moira Chan-Yeung and Elaine Fuertes and Ulrike Gehring and Anna Gref and Joachim Heinrich and Marie Standl and Irina Lehmann and Marjan Kerkhof and Koppelman, {Gerard H} and Kozyrskyj, {Anita L} and G{\"o}ran Pershagen and Christopher Carlsten and Ursula Kr{\"a}mer and Tamara Schikowski and {TAG Study Group}",

note = "{\textcopyright} 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.",

year = "2018",

month = sep,

doi = "10.1111/pai.12903",

language = "English",

volume = "29",

pages = "596--605",

journal = "Pediatric Allergy and Immunology",

issn = "0905-6157",

publisher = "Blackwell Munksgaard",

number = "6",

}

Hüls, A, Klümper, C, MacIntyre, EA, Brauer, M, Melén, E, Bauer, M, Berdel, D, Bergström, A, Brunekreef, B, Chan-Yeung, M, Fuertes, E, Gehring, U, Gref, A, Heinrich, J, Standl, M, Lehmann, I, Kerkhof, M, Koppelman, GH, Kozyrskyj, AL, Pershagen, G, Carlsten, C, Krämer, U, Schikowski, T & TAG Study Group 2018, 'Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life', Pediatric Allergy and Immunology, vol. 29, no. 6, pp. 596-605. https://doi.org/10.1111/pai.12903

TY - JOUR

T1 - Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life

AU - Hüls, Anke

AU - Klümper, Claudia

AU - MacIntyre, Elaina A

AU - Brauer, Michael

AU - Melén, Erik

AU - Bauer, Mario

AU - Berdel, Dietrich

AU - Bergström, Anna

AU - Brunekreef, Bert

AU - Chan-Yeung, Moira

AU - Fuertes, Elaine

AU - Gehring, Ulrike

AU - Gref, Anna

AU - Heinrich, Joachim

AU - Standl, Marie

AU - Lehmann, Irina

AU - Kerkhof, Marjan

AU - Koppelman, Gerard H

AU - Kozyrskyj, Anita L

AU - Pershagen, Göran

AU - Carlsten, Christopher

AU - Krämer, Ursula

AU - Schikowski, Tamara

AU - TAG Study Group

PY - 2018/9

Y1 - 2018/9

N2 - BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation.METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP.RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population.CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.

AB - BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation.METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP.RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population.CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.

KW - atopic eczema

KW - gene-environment interaction

KW - weighted genetic risk scores

U2 - 10.1111/pai.12903

DO - 10.1111/pai.12903

M3 - Article

C2 - 29624745

SN - 0905-6157

VL - 29

SP - 596

EP - 605

JO - Pediatric Allergy and Immunology

JF - Pediatric Allergy and Immunology

IS - 6

ER -

Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life

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Keywords

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