PMID- 20802163

OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR - 20211020
IS - 1535-4970 (Electronic)
IS - 1073-449X (Print)
IS - 1073-449X (Linking)
VI - 183
IP - 2
DP - 2011 Jan 15
TI - Genetic variation in the glutathione synthesis pathway, air pollution, and
children's lung function growth.
PG - 243-8
LID - 10.1164/rccm.201006-0849OC [doi]
AB - 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.

FAU - Breton, Carrie V
AU - Breton CV
AD - Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar
Street, CHP 236, Los Angeles, CA 90033, USA. breton@usc.edu
FAU - Salam, Muhammad T
AU - Salam MT
FAU - Vora, Hita
AU - Vora H
FAU - Gauderman, W James
AU - Gauderman WJ
FAU - Gilliland, Frank D
AU - Gilliland FD
LA - eng
GR - P30 ES007048/ES/NIEHS NIH HHS/United States
GR - 5R01HL61768/HL/NHLBI NIH HHS/United States
GR - 5P01 ES011627/ES/NIEHS NIH HHS/United States
GR - 1R01HL76647/HL/NHLBI NIH HHS/United States
GR - 5P01 ES009581/ES/NIEHS NIH HHS/United States
GR - R826708-01/PHS HHS/United States
GR - RD831861-01/RD/ORD VA/United States
GR - 5P30 ES007048/ES/NIEHS NIH HHS/United States
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
DEP - 20100827
TA - Am J Respir Crit Care Med
JT - American journal of respiratory and critical care medicine
JID - 9421642
RN - GAN16C9B8O (Glutathione)
SB - IM
MH - Air Pollution/*adverse effects
MH - California
MH - Child
MH - Cohort Studies
MH - Environmental Exposure
MH - Female
MH - Follow-Up Studies
MH - Forced Expiratory Flow Rates/genetics
MH - Forced Expiratory Volume/genetics
MH - Genetic Predisposition to Disease/genetics
MH - Glutathione/*biosynthesis/*genetics
MH - Humans
MH - Lung/growth & development/*physiopathology
MH - Lung Diseases/*etiology/physiopathology
MH - Male
MH - Oxidative Stress
MH - Polymorphism, Single Nucleotide/*genetics
MH - Prospective Studies
MH - Respiratory Function Tests/methods
PMC - PMC3040392
EDAT- 2010/08/31 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/08/31 06:00
PHST- 2010/08/31 06:00 [entrez]
PHST- 2010/08/31 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - 201006-0849OC [pii]
AID - ajrccm1832243 [pii]
AID - 10.1164/rccm.201006-0849OC [doi]
PST - ppublish
SO - Am J Respir Crit Care Med. 2011 Jan 15;183(2):243-8. doi:
10.1164/rccm.201006-0849OC. Epub 2010 Aug 27.