Elsevier

The Journal of Pediatrics

Volume 154, Issue 3, March 2009, Pages 401-408.e1
The Journal of Pediatrics

Original article
Associations between Multiple Environmental Exposures and Glutathione S-transferase P1 on Persistent Wheezing in a Birth Cohort

https://doi.org/10.1016/j.jpeds.2008.08.040Get rights and content

Objective

To determine the impact of environmental exposures (diesel exhaust particle [DEP], environmental tobacco smoke [ETS], and mold) that may contribute to oxidative stress on persistent wheezing in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort and to determine how the impact of these exposures is modified by the GST-P1 Ile105Val polymorphism.

Study design

A land-use regression model was used to derive an estimate of each child's DEP exposure. ETS exposure was determined by questionnaire data. Each child's home was evaluated for visible mold by a trained professional. Children in the CCAAPS cohort were genotyped for the GST-P1 polymorphism (n = 570). Persistent wheezing was defined as wheezing at both 12 and 24 months.

Results

High DEP exposure conferred increased risk for wheezing phenotypes but only among the Val105 allele carriers. Infants with multiple exposures were significantly more likely to persistently wheeze despite their genotype.

Conclusion

There is evidence for an environmental effect of DEP among carriers of the GST-P1 Val105 allele in the development of persistent wheezing in children. The protective effect of the GST-P1 Ile105 genotype may be overwhelmed by multiple environmental exposures that converge on oxidative stress pathways.

Section snippets

Study Participants

The CCAAPS study is a longitudinal birth cohort of high-risk children having at least 1 atopic parent. A complete description of the study's recruitment, methods, and objectives has been published.17 Briefly, infants with at least 1 atopic parent (on the basis of allergy skin prick testing) were enrolled between 2001 and 2003 in a 7-county area of Cincinnati, Ohio. Families were recruited on the basis of the proximity of their home residence to truck and bus traffic by geocoding residential

Subjects, Exposures, and Health Outcomes

Of the 570 study participants, 464 (81.4%) infants were Caucasian, and 106 (18.6%) were non-Caucasian (Table I). Of the non-Caucasian infants, 86.8% were African Americans defined as both parents being African American. Non-Caucasian infants were significantly more likely than Caucasians to have a household income less than $40 000 (69.5% vs 26.7%; P < .001), have higher exposure to DEP ≥0.50 μg/m3 (P < .001), and have visible mold in their homes (P = .01). ETS exposure did not significantly

Discussion

To our knowledge, this study is the first to investigate the impact of complex environmental exposures (DEP, ETS, and mold) along with genetics, specifically GST-P1 on persistent wheezing in children. Our data support that DEP, ETS, or mold exposure are risk factors for wheezing by 24 months of age. Furthermore, the presence of the Val105 allele, which has been shown to significantly lower GST enzyme activity,16 confers susceptibility to these environmental exposures compared with the Ile105

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    Supported by NIEHS R01 ES11170 and ES10957. The authors declare no conflicts of interest.

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