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

• Published in: Pediatric allergy and immunology Vol. 29; no. 6; pp. 596 - 605
• Main Authors: Hüls, Anke, Klümper, Claudia, MacIntyre, Elaina A., Brauer, Michael, Melén, Erik, Bauer, Mario, Berdel, Dietrich, Bergström, Anna, Brunekreef, Bert, Chan‐Yeung, Moira, Fuertes, Elaine, Gehring, Ulrike, Gref, Anna, Heinrich, Joachim, Standl, Marie, Lehmann, Irina, Kerkhof, Marjan, Koppelman, Gerard H., Kozyrskyj, Anita L., Pershagen, Göran, Carlsten, Christopher, Krämer, Ursula, Schikowski, Tamara
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2018
• Subjects: Age; Air pollution; Atopic dermatitis; atopic eczema; Birth; Children; Dermatitis; Eczema; Genetic diversity; Genetic effects; Genetic variance; gene‐environment interaction; Glutathione transferase; Inflammation; Medicin och hälsovetenskap; Nitrogen dioxide; Oxidative stress; Pollution; Population genetics; Single-nucleotide polymorphism; TLR2 protein; TLR4 protein; Toll-like receptors; Tumor necrosis factor; weighted genetic risk scores; atopic eczema; gene-environment interaction; weighted genetic risk scores
• ISSN: 0905-6157; 1399-3038; 1399-3038
• DOI: 10.1111/pai.12903

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.