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 GSTM5 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 FEV(1) 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.
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 GSTM5 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 FEV(1) 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.
Authors: F D Gilliland; K Berhane; R McConnell; W J Gauderman; H Vora; E B Rappaport; E Avol; J M Peters Journal: Thorax Date: 2000-04 Impact factor: 9.139
Authors: Dmitri V Zaykin; Peter H Westfall; S Stanley Young; Maha A Karnoub; Michael J Wagner; Margaret G Ehm Journal: Hum Hered Date: 2002 Impact factor: 0.444
Authors: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: W James Gauderman; G Frank Gilliland; Hita Vora; Edward Avol; Daniel Stram; Rob McConnell; Duncan Thomas; Fred Lurmann; Helene G Margolis; Edward B Rappaport; Kiros Berhane; John M Peters Journal: Am J Respir Crit Care Med Date: 2002-07-01 Impact factor: 21.405
Authors: Lori J Manzel; Lei Shi; Patrick T O'Shaughnessy; Peter S Thorne; Dwight C Look Journal: Am J Respir Cell Mol Biol Date: 2010-03-26 Impact factor: 6.914
Authors: Fritz Horak; Tamas Fazekas; Angela Zacharasiewicz; Ernst Eber; Herbert Kiss; Alfred Lichtenschopf; Manfred Neuberger; Rudolf Schmitzberger; Burkhard Simma; Andree Wilhelm-Mitteräcker; Josef Riedler Journal: Wien Klin Wochenschr Date: 2011-12-22 Impact factor: 1.704
Authors: Pingye Zhang; Juan Pablo Lewinger; David Conti; John L Morrison; W James Gauderman Journal: Genet Epidemiol Date: 2016-05-27 Impact factor: 2.135
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