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


CONCLUSIONS
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.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. reajr@channing.harvard.edu
A J
AJ
Rogers
C
C
Brasch-Andersen
I
I
Ionita-Laza
A
A
Murphy
S
S
Sharma
B J
BJ
Klanderman
B A
BA
Raby
D001249:Asthma / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D018628:Gene Dosage / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D010641:Phenotype; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D005982:Glutathione Transferase; D014028:Tobacco Smoke Pollution