The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma
Article first published online: 21 OCT 2009
© 2009 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 39, Issue 11, pages 1721–1729, November 2009
How to Cite
Rogers, A. J., Brasch-Andersen, C., Ionita-Laza, I., Murphy, A., Sharma, S., Klanderman, B. J. and Raby, B. A. (2009), The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma. Clinical & Experimental Allergy, 39: 1721–1729. doi: 10.1111/j.1365-2222.2009.03372.x
- Issue published online: 21 OCT 2009
- Article first published online: 21 OCT 2009
- Submitted 11 May 2009; revised 29 July 2009; accepted 10 August 2009
- copy number variation (CNV);
- intrauterine smoke exposure;
- tobacco smoke
Background The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress.
Objective To explore the joint interactive effects of GSTM1 copy number and tobacco smoke exposure on the development of asthma and asthma-related phenotypes in a family-based cohort of childhood asthmatics.
Methods We performed quantitative PCR-based genotyping for GSTM1 copy number in children of self-reported white ancestry with mild to moderate asthma in the Childhood Asthma Management Program. Questionnaire data regarding intrauterine (IUS) and post-natal, longitudinal smoke exposure were available. We performed both family-based and population-based tests of association for the interaction between GSTM1 copy number and tobacco smoke exposure with asthma and asthma-related phenotypes.
Results Associations of GSTM1-null variants with asthma (P=0.03), younger age of asthma symptom onset (P=0.03), and greater airflow obstruction (reduced forced expiratory volume in 1 s / forced vital capacity, P=0.01) were observed among the 50 children (10% of the cohort) with exposure to IUS. In contrast, no associations were observed between GSTM1-null variants and asthma-related phenotypes among children without IUS exposure. Presence of at least one copy of GSTM1 conferred protection.
Conclusion These findings support an important gene-by-environment interaction between two common factors: increased risk of asthma and asthma-related phenotypes conferred by GSTM1-null homozygosity in children is restricted to those with a history of IUS exposure.