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a Population Pharmacogenetics Group, Biomedical Research Centre
b Division of Medicine and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom
c Children's Asthma and Allergy Research Unit, University of Dundee
d Directorate of Pediatrics, National Health Service Tayside, Ninewells Hospital, Dundee and Perth Royal Infirmary, Perth, Scotland, United Kingdom
OBJECTIVES. Our purpose with this work was to assess the contribution of glutathione S-transferase gene variants to asthma susceptibility and pulmonary function in relation to tobacco smoke exposure in the home.
METHODS. Young individuals with asthma (age: 321 years; n = 504) were recruited through primary and secondary care throughout Tayside, Scotland (BREATHE Study). Spirometry was obtained on 407 individuals. Binary logistic regression and general linear modeling were used to explore phenotypic characteristics by genotype and tobacco smoke exposure status in younger children (312 years; n = 384) and teenagers and young adults (1321 years; n = 120).
RESULTS. Three- to 12-year-olds with asthma, null for the GSTM1 gene or homozygous for the GSTP1Val105 allele, were overrepresented in the group exposed to environmental tobacco smoke. No differences in lung function values could be detected in this group. In contrast, 13- to 21-year-olds with the GSTM1-null genotype or homozygous for the GSTP1Val105 allele from smoking households were more likely to have a substantially lower percentage of predicted peak expiratory flow rates than those from nonsmoking households (83% vs 98%).
CONCLUSIONS. Three- to 12-year-olds who are null for GSTM1 or homozygous for the GSTP1Val105 allele are more susceptible to asthma associated with environmental tobacco smoke exposure than those with more intact glutathione S-transferase status. In the 13- to 21-year-olds, GSTM1-null status interacts with environmental tobacco smoke exposure to substantially reduce peak expiratory flow rate. The environmental tobacco smoke effect in GSTM1-null children with asthma could be cumulative over time, resulting in detrimental effects on peak expiratory flow rate in 13- to 21-year-olds with asthma.
Key Words: asthma child glutathione S-transferase smoking pulmonary function peak expiratory flow
Abbreviations: GSTglutathione S-transferase ETSenvironmental tobacco smoke PEFRpeak expiratory flow rate FEV1forced expiratory volume in 1 second FVCforced vital capacity ORodds ratio CIconfidence interval
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