Published online August 1, 2006
PEDIATRICS Vol. 118 No. 2 August 2006, pp. 710-716 (doi:10.1542/peds.2005-3030)
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ARTICLE

Glutathione S-Transferase M1 and P1 Genotype, Passive Smoking, and Peak Expiratory Flow in Asthma

Colin N.A. Palmer, PhDa, Alex S.F. Doney, PhDb, Simon P. Lee, MSca, Inez Murrie, MScc, Tahmina Ismail, MScc, Donald F. Macgregor, FRCPCHc,d and Somnath Mukhopadhyay, MD, PhD, FRCPHc

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: 3–21 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 (3–12 years; n = 384) and teenagers and young adults (13–21 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: GST—glutathione S-transferase • ETS—environmental tobacco smoke • PEFR—peak expiratory flow rate • FEV1—forced expiratory volume in 1 second • FVC—forced vital capacity • OR—odds ratio • CI—confidence interval


Accepted Feb 16, 2006.




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