RATIONALE: Glutathione plays an important role in antioxidant and inflammatory processes in the lung. Alterations in glutathione metabolism are a central feature of several chronic lung diseases. OBJECTIVES: To determine whether sequence variation in genes in the glutathione synthesis pathway alters susceptibility to air pollution effects on lung function. METHODS: In this prospective study, 14,821 lung function measurements were taken on 2,106 children from 12 Southern California cities. Tagging single-nucleotide polymorphisms in glutathione metabolism pathway genes GSS, GSR, GCLM, and GCLC were genotyped by GoldenGate assay (Illumina, San Diego, CA). Mixed regression models were used to determine whether particular haplotypes were associated with FEV(1), maximal mid-expiratory flow rate, and FVC and whether any of the genetic associations varied with levels of exposure to air pollutants. MEASUREMENTS AND MAIN RESULTS: We found that variation in the GSS locus was associated with differences in susceptibility of children for lung function growth deficits associated with NO(2), PM(10), PM(2.5), elemental carbon, organic carbon, and O(3). The negative effects of air pollutants were largely observed within participants who had a particular GSS haplotype. The effects ranged from -124.2 to -149.1 for FEV(1), from -92.9 to -126.7 for FVC, and from -193.9 to -277.9 for maximal mid-expiratory flow rate for all pollutants except O(3), which showed a larger decrease in lung function in children without this haplotype. CONCLUSIONS: Variation in GSS was associated with differences in susceptibility to adverse effects of pollutants on lung function growth.
RATIONALE: Glutathione plays an important role in antioxidant and inflammatory processes in the lung. Alterations in glutathione metabolism are a central feature of several chronic lung diseases. OBJECTIVES: To determine whether sequence variation in genes in the glutathione synthesis pathway alters susceptibility to air pollution effects on lung function. METHODS: In this prospective study, 14,821 lung function measurements were taken on 2,106 children from 12 Southern California cities. Tagging single-nucleotide polymorphisms in glutathione metabolism pathway genes GSS, GSR, GCLM, and GCLC were genotyped by GoldenGate assay (Illumina, San Diego, CA). Mixed regression models were used to determine whether particular haplotypes were associated with FEV(1), maximal mid-expiratory flow rate, and FVC and whether any of the genetic associations varied with levels of exposure to air pollutants. MEASUREMENTS AND MAIN RESULTS: We found that variation in the GSS locus was associated with differences in susceptibility of children for lung function growth deficits associated with NO(2), PM(10), PM(2.5), elemental carbon, organic carbon, and O(3). The negative effects of air pollutants were largely observed within participants who had a particular GSS haplotype. The effects ranged from -124.2 to -149.1 for FEV(1), from -92.9 to -126.7 for FVC, and from -193.9 to -277.9 for maximal mid-expiratory flow rate for all pollutants except O(3), which showed a larger decrease in lung function in children without this haplotype. CONCLUSIONS: Variation in GSS was associated with differences in susceptibility to adverse effects of pollutants on lung function growth.
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; Edward Avol; Frank Gilliland; Hita Vora; Duncan Thomas; Kiros Berhane; Rob McConnell; Nino Kuenzli; Fred Lurmann; Edward Rappaport; Helene Margolis; David Bates; John Peters Journal: N Engl J Med Date: 2004-09-09 Impact factor: 91.245
Authors: J M Peters; E Avol; W J Gauderman; W S Linn; W Navidi; S J London; H Margolis; E Rappaport; H Vora; H Gong; D C Thomas Journal: Am J Respir Crit Care Med Date: 1999-03 Impact factor: 21.405
Authors: J M Peters; E Avol; W Navidi; S J London; W J Gauderman; F Lurmann; W S Linn; H Margolis; E Rappaport; H Gong; D C Thomas Journal: Am J Respir Crit Care Med Date: 1999-03 Impact factor: 21.405
Authors: Elisabet Johansson; Scott C Wesselkamper; Howard G Shertzer; George D Leikauf; Timothy P Dalton; Ying Chen Journal: Biochem Biophys Res Commun Date: 2010-04-22 Impact factor: 3.575
Authors: Dean E Schraufnagel; John R Balmes; Clayton T Cowl; Sara De Matteis; Soon-Hee Jung; Kevin Mortimer; Rogelio Perez-Padilla; Mary B Rice; Horacio Riojas-Rodriguez; Akshay Sood; George D Thurston; Teresa To; Anessa Vanker; Donald J Wuebbles Journal: Chest Date: 2018-11-09 Impact factor: 9.410
Authors: Hui Zhou; Xia Iona Li; Jeong Hee Kim; Muhammad T Salam; Hyo Bin Kim; Rob S McConnell; Rima Habre; Tracy Bastain; Shohreh F Farzan; Jill Johnston; Frank D Gilliland Journal: Ann Allergy Asthma Immunol Date: 2017-12-06 Impact factor: 6.347