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

Abstract

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 Val 105 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 Val 105 allele in the development of persistent wheezing in children. The protective effect of the © 2008 Mosby, Inc. All rights reserved.Correspondence should be addressed to: Gurjit K. Khurana Hershey, M.D., Ph.D., Institute for Personalized and Predictive Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC 7037, Cincinnati, Phone: (513) Fax: (513) 636-1657; E-mail: Gurjit.Hershey@cchmc.org . Edited by Padbury and WFBPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Delineating the factors that are contributory or protective to persistent wheezing in early childhood is critical to advance our understanding of asthma. There is limited information about how genetic and environmental factors interact to influence longitudinal asthmatic/wheezing status over time. DEP, ETS, and mold exposures are common and each has been shown to aggravate respiratory symptoms. The gene-environment effect related to these individual and/ or combined exposures has not been evaluated with regard to longitudinal wheezing status. The purpose of this study was to investigate whether exposure to DEP, ETS, and/or mold uniquely modifies wheezing and persistent wheezing in young children, especially among those with the GST-P1 I105V polymorphism. Our study evaluates the modified effect of this polymorphism upon exposure to not only ETS and mold, but distinctively DEP exposure associated with traffic and their combined exposures utilizing the well-characterized Cincinnati Childhood Allergy and Air Pol...

Association between domestic mould and mould components, and asthma and allergy in children: a systematic review

“…Visible mould exposure Wheeze Of the nine publications evaluating the longitudinal effect of early exposure to visible mould at home and wheezing in the first 3 yrs of life, seven studies observed a significant positive association [8,12,36,41,42,48,49]. In one US birth cohort study (the Cincinnati Childhood Allergy and Air Pollution Study) from IOSSIFOVA et al [8], the reported increase in risk was persistent from 1-3 yrs of age.…”

Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort

“…Children who were homozygous (+/+) or heterozygous (−/+) for GSTM1 (or GSTT1) were classified as GSTM1 (GSTT1) positive, and those who were homozygous deleted (−/−) were classified as GSTM1 (GSTT1) null. Modification of the association between acetaminophen and wheeze by the presence of the minor allele in GSTP1 (ie, Ile/Val or Val/Val) was evaluated based on (1) previous associations with asthma11 13 and (2) altered conjugation kinetics of toxicants related to asthma among individuals with this genotype 15…”

The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy

“…30 High diesel exhaust particles increase the risk for wheezing only in children with the GSTP1 rs 1695 G allele. 31 Our finding that prenatal exposure to home renovation elevated CB IgE levels in neonates with GSTP1 G or NRF2 A alleles from atopic mothers suggests that prenatal exposure to home renovation may induce T-cell differentiation to Th2 through oxidative stress. Interestingly, the finding that gene-environment interactions are only present in the offspring from atopic mothers suggests that the maternal atopic status may modify the interactions between genetic polymorphisms of reactive oxygen specifies and prenatal exposure to home renovation through another interaction with atopy-related genes of neonates inherited from atopic mothers or via the intrauterine environment provided by atopic mothers.…”