Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 179, Issue 7, Pages 601-607Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200809-1384OC
Keywords
FEV1; in utero; glutathione S-transferase; tobacco smoke
Categories
Funding
- National Institute of Environmental Health Sciences [5P01 ES009581, 5P01 ES011627, 5P30 ES007048]
- United States Environmental Protection Agency [8826708-01, RD831861-01]
- National Heart, Lung and Blood Institute [5R01 HL61768, 1 R01 HL76647]
- Hastings Foundation
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Rationale: The glutathione S-transferases (GSTs) are important detoxification enzymes. Objectives: To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure. Methods: In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts. For each child, tagging single nucleotide polymorphisms in GSTM2, GSTM3, GSTM4, and GSTMS loci were genotyped. Using principal components and haplotype analyses, the significance of each locus in relation to level and growth of FEV1, maximum midexpiratory flow rate (MMEF), and FVC was evaluated. Interactions between loci and tobacco smoke on lung function were also investigated. Measurements and Main Results: Variation in the GST mu family locus was associated with lower FEV1 (P = 0.01) and MMEF (0.04). Two haplotypes of GSTM2 were associated with FEV1 and MMEF, with effect estimates in opposite directions. One haplotype in GSTM3 showed a decrease in growth for MMEF (-164.9 ml/s) compared with individuals with other haplotypes. One haplotype in GSTM4 showed significantly decreased growth in FEV1 (-51.3 ml), MMEF (-69.1 ml/s), and FVC (-44.4 ml), compared with all other haplotypes. These results were consistent across two independent cohorts. Variation in GSTM2 was particularly important for FVC and FEV1 among children whose mothers smoked during pregnancy. Conclusions: Genetic variation across the GST mu locus is associated with 8-year lung function growth. Children of mothers who smoked during pregnancy and had variation in GSTM2 had lower lung function growth.
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