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.
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.
Authors: Stanley Szefler; Scott Weiss; James Tonascia; N Franklin Adkinson; Bruce Bender; Reuben Cherniack; Michele Donithan; H William Kelly; Joseph Reisman; Gail G Shapiro; Alice L Sternberg; Robert Strunk; Virginia Taggart; Mark Van Natta; Robert Wise; Margaret Wu; Robert Zeiger Journal: N Engl J Med Date: 2000-10-12 Impact factor: 91.245
Authors: Frank D Gilliland; Yu-Fen Li; Louis Dubeau; Kiros Berhane; Edward Avol; Rob McConnell; W James Gauderman; John M Peters Journal: Am J Respir Crit Care Med Date: 2002-08-15 Impact factor: 21.405
Authors: Frank D Gilliland; W James Gauderman; Hita Vora; Edward Rappaport; Louis Dubeau Journal: Am J Respir Crit Care Med Date: 2002-09-01 Impact factor: 21.405
Authors: I Romieu; J J Sienra-Monge; M Ramírez-Aguilar; H Moreno-Macías; N I Reyes-Ruiz; B Estela del Río-Navarro; M Hernández-Avila; S J London Journal: Thorax Date: 2004-01 Impact factor: 9.139
Authors: H W Chu; C M Lloyd; W Karmaus; P Maestrelli; P Mason; G Salcedo; J Thaikoottathil; A J Wardlaw Journal: Clin Exp Allergy Date: 2010-11 Impact factor: 5.018
Authors: Maria José Rosa; Kyung Hwa Jung; Matthew S Perzanowski; Elizabeth A Kelvin; Katherine W Darling; David E Camann; Steven N Chillrud; Robin M Whyatt; Patrick L Kinney; Frederica P Perera; Rachel L Miller Journal: Respir Med Date: 2010-12-15 Impact factor: 3.415
Authors: A J Rogers; J-H Chu; K Darvishi; I Ionita-Laza; H Lehmann; R Mills; C Lee; B A Raby Journal: Clin Exp Allergy Date: 2013-04 Impact factor: 5.018