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The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

Authors

  • A. J. Rogers,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA,
    2. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA,
    3. Harvard Medical School, Boston, MA, USA,
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  • C. Brasch-Andersen,

    1. Department of Biochemistry, Pharmacology, and Genetics, Odense University Hospital, Odense, Denmark,
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  • I. Ionita-Laza,

    1. Harvard Medical School, Boston, MA, USA,
    2. Harvard School of Public Health, Boston, MA, USA and
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  • A. Murphy,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA,
    2. Harvard Medical School, Boston, MA, USA,
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  • S. Sharma,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA,
    2. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA,
    3. Harvard Medical School, Boston, MA, USA,
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  • B. J. Klanderman,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA,
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  • B. A. Raby

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA,
    2. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA,
    3. Harvard Medical School, Boston, MA, USA,
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Correspondence:
Angela J. Rogers, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
E-mail: reajr@channing.harvard.edu
Cite this as: A.Rogers,C. Brasch-Andersen,I. Ionita-Laza,A. Murphy,S. Sharma,B. Klanderman andB. Raby, Clinical & Experimental Allergy, 2009 (39) 1121–1729.

Summary

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.

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