Academic journal article Environmental Health Perspectives

Interactions between Glutathione S-Transferase P1, Tumor Necrosis Factor, and Traffic-Related Air Pollution for Development of Childhood Allergic Disease

Academic journal article Environmental Health Perspectives

Interactions between Glutathione S-Transferase P1, Tumor Necrosis Factor, and Traffic-Related Air Pollution for Development of Childhood Allergic Disease

Article excerpt

BACKGROUND: Air pollutants may induce airway inflammation and sensitization due to generation of reactive oxygen species. The genetic background to these mechanisms could be important effect modifiers.

OBJECTIVE: Our goal was to assess interactions between exposure to air pollution and single nucleotide polymorphisms (SNPs) in the [beta] 2-adrenergic receptor (ADRB2), glutathione S-transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of childhood allergic disease.

METHODS: In a birth cohort originally of 4,089 children, we assessed air pollution from local traffic using nitrogen oxides (traffic [NO.sub.x] as an indicator based on emission databases and dispersion modeling and estimated individual exposure though geocoding of home addresses. We measured peak expiratory flow rates and specific IgE for inhalant and food allergens at 4 years of age, and selected children with asthma symptoms up to 4 years of age (n = 542) and controls (n = 542) for genotyping.

RESULTS: Interaction effects on allergic sensitization were indicated between several GSTPl SNPs and traffic [NO.sub.x] exposure during the first year of life [P.sub.nominal] < 0.001-0.06).Pnominal < 0.001-0.06). Children with Ile105Val/Val105Val genotypes were at increased risk of sensitization to any allergen when exposed to elevated levels of traffic [NO.sub.x] (for a difference between the 5th and 95th percentile of exposure: odds ratio = 2.4; 95% confidence interval, 1.0-5.3). In children with TNF-308 GA/AA genotypes, the GSTPI-[NO.sub.x] interaction effect was even more pronounced. We observed no conclusive interaction effects for ADRB2.

CONCLUSION: The effect of air pollution from traffic on childhood allergy appears to be modified by GSTP1 and TNF variants, supporting a role of genes controlling the antioxidative system and inflammatory response in allergy.

KEY WORDS: ADRB2, air pollution, allergy, asthma, genetics, GSTPl, interaction, nitrogen oxides, polymorphism, TNF. Environ Health Perspect 116:1077-1084 (2008). doi:10.1289/ehp.11117 available via [Online 25 March 2008]

Asthma and allergy are complex diseases in which numerous genetic and environmental factors play a role in the etiology. Air pollutants, including vehicle-related pollutants such as particles and nitrogen oxides ([NO.sub.x]), are known to induce airway inflammation and increase airway responsiveness (Gilmour et al. 2006; Grievink et al. 2000). It is plausible that genetic variants in the genes controlling the inflammatory and antioxidative systems may determine whether exposure to air pollutants will promote the development of allergic diseases. Identification of such gene-environment interactions may hold the key to understanding the great variability among individuals in responses to various environmental factors, among them environmental tobacco smoke, ozone, and diesel exhaust particles (London 2007).

The inflammatory response after exposure to air pollutants is maintained by the activation of proinflammatory molecules and may also induce lung damage due to generation of reactive oxygen species (MacNee 2001). Further, diesel exhaust particles may induce IgE responses directly by acting on B-cells and enhancing the production of cytokines that favor the development of an allergy-prone immune response (Sydbom et al. 2001).

Members of the glurathione S-transferase (GST) supergene family have been a particular focus of studies of gene-environment interactions, because they constitute an intracellular protective system against electrophiles and the formation of hazardous reactive oxygen species (Hayes and Strange 1995; McCunney 2005; Strange et al. 2001). Recent studies support the presence of gene--environment interaction, or effect modification, between exposure to air pollutants and gluththione S-transferase P1 (GSTP1) variants, especially the isoleucine (Ile)/valine (Val) polymorphism at amino acid position 105 with respect to childhood asthma and nasal allergic responses (Gilliland et al. …

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