Genetic susceptibility to the respiratory effects of air pollution (original) (raw)
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Genetic susceptibility to airway inflammation and exposure to short-term outdoor air pollution
Environmental Health
Background Air pollution is a large environmental health hazard whose exposure and health effects are unequally distributed among individuals. This is, at least in part, due to gene-environment interactions, but few studies exist. Thus, the current study aimed to explore genetic susceptibility to airway inflammation from short-term air pollution exposure through mechanisms of gene-environment interaction involving the SFTPA, GST and NOS genes. Methods Five thousand seven hundred two adults were included. The outcome measure was fraction of exhaled nitric oxide (FeNO), at 50 and 270 ml/s. Exposures were ozone (O3), particulate matter < 10 µm (PM10), and nitrogen dioxide (NO2) 3, 24, or 120-h prior to FeNO measurement. In the SFTPA, GST and NOS genes, 24 single nucleotide polymorphisms (SNPs) were analyzed for interaction effects. The data were analyzed using quantile regression in both single-and multipollutant models. Results Significant interactions between SNPs and air pollutio...
American Journal of Epidemiology, 2013
Variants of inflammatory and immune response genes have been associated with adverse respiratory outcomes following exposure to air pollution. However, the genes involved and their associations are not well characterized, and there has been no systematic review. Thus, we conducted a review following the guidelines of the Human Genome Epidemiology Network. Six observational studies and 2 intervention studies with 14,903 participants were included (2001-2010). Six studies showed at least 1 significant gene-pollutant interaction. Meta-analysis was not possible due to variations in genes, pollutants, exposure estimates, and reported outcomes. The most commonly studied genes were tumor necrosis factor α (TNFA) (n = 6) and toll-like receptor 4 (TLR4) (n = 3). TNFA-308G>A modified the action of ozone and nitrogen dioxide on lung function, asthma risk, and symptoms; however, the direction of association varied between studies. The TLR4 single-nucleotide polymorphisms rs1927911, rs10759931, and rs6478317 modified the association of particulate matter and nitrogen dioxide with asthma. The transforming growth factor β1 (TGFB1) polymorphism-509C>T also modified the association of pollutants with asthma. This review indicates that genes controlling innate immune recognition of foreign material (TLR4) and the subsequent inflammatory response (TGFB1, TLR4) modify the associations of exposure to air pollution with respiratory function. The associations observed have biological plausibility; however, larger studies with improved reporting are needed to confirm these findings.
Association of Tumor Necrosis Factor-α Polymorphisms and Ozone-induced Change in Lung Function
American Journal of Respiratory and Critical Care Medicine, 2005
Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-␣ (TNF), lymphotoxin-␣ (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV 1 with ozone challenge, as a percentage of baseline, was Ϫ3% in TNF Ϫ308G/A or A/A individuals, compared with Ϫ9% in G/G individuals (p ϭ 0.024). When considering TNF haplotypes, the smallest change in FEV 1 with ozone exposure was associated with the TNF haplotype comprising LTA ϩ252G/TNF Ϫ1031T/TNF Ϫ308A/TNF Ϫ238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p ϭ 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozoneinduced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.
Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes
European Respiratory Journal, 2007
Chronic exposure to ozone (O 3) can cause changes in lung function that may reflect remodelling of small airways. It is likely that antioxidant enzyme function affects susceptibility to O 3. The aim of the present study was to determine whether polymorphisms in antioxidant enzyme (GSTM1, GSTP1 and NQO1) genes affect the risk of lung function changes related to chronic exposure to O 3. In total, 210 young adults who participated in a previous study, which showed a relationship between lifetime exposure to O 3 and decreased lung function, were genotyped. Multivariable linear regression was used to model sex-specific associations between genotypes and O 3-related lung function changes, adjusting for height, weight, lifetime exposure to nitrogen dioxide and particles with a 50% cutoff aerodynamic diameter of 10 mm, and self-identified race/ethnicity. The GSTM1-null/NQO1 Pro187Pro-combination genotype was significantly associated with increased risk of an O 3-related decrease in mean forced expiratory flow between 25-75% of forced vital capacity in females (parameter estimate¡SE-75¡35 mL?s-1), while the GSTP1 Val105 variant genotypes were significantly associated with greater risk of an O 3-related decrease in mean forced expiratory flow at 75% of forced vital capacity in males (-81¡31 mL?s-1). GSTM1-null status was not significantly associated with any O 3-related changes in lung function in either sex. The current authors conclude that the effects of antioxidant enzyme gene polymorphisms on the risk of decreased lung function related to chronic exposure to ozone may be modified by sexspecific factors.
Gene by environment interaction and ambient air pollution
2010
Epidemiologic studies have clearly shown that air pollution is associated with a range of respiratory effects. Recent research has identified oxidative stress as a major biologic pathway underlying the toxic effect of air pollutants. Genetic susceptibility is likely to play a role in response to air pollution. Genes involved in oxidative stress and inflammatory pathways are logical candidates for the study of the interaction with air pollutants. In this article we use the example of asthma, a genetically complex disease, to address the issue of gene by environment interaction with air pollution. The majority of studies have focused on the genes GSTM1, GSTP1, NQO1, and TNF, but the inconsistency of the results prevents the drawing of firm conclusions. The limited sample size of most studies to date make them underpowered for the study of gene by gene interactions. Large consortia of studies with repeated measurements of environmental exposures and clear phenotypic assessments may help determine special environmental triggers and the window of susceptibility in the development of atopy and asthma. The role of gene by gene interactions and epigenetic mechanisms needs to be considered along with gene by environment interactions.
Thorax, 2004
We recently reported that antioxidant supplementation with vitamins C and E mitigated ozone related decline in forced expiratory flow (FEF(25-75)) in 158 asthmatic children in an area with high ozone exposure in Mexico City. A study was undertaken to determine whether deletion of glutathione S-transferase M1 (GSTM1 null genotype), a gene involved in response to oxidative stress, influences ozone related decline in FEF(25-75) and the benefit of antioxidant supplementation. GSTM1 null children receiving placebo had significant ozone related decrements in FEF(25-75) (percentage change per 50 ppb of ozone 2.9 (95% CI -5.2 to -0.6), p=0.01); GSTM1 positive children did not. Conversely, the effect of antioxidants was stronger in children with the GSTM1 null genotype. Asthmatic children with a genetic deficiency of GSTM1 may be more susceptible to the deleterious effects of ozone on the small airways and might derive greater benefit from antioxidant supplementation.
Ozone, Oxidant Defense Genes, and Risk of Asthma during Adolescence
American Journal of Respiratory and Critical Care Medicine, 2008
Rationale: Although oxidative stress is a cardinal feature of asthma, the roles of oxidant air pollutants and antioxidant genes Heme oxygenase1 (HMOX1), catalase (CAT) and manganese superoxide dismutase (MNSOD) in asthma pathogenesis have yet to be determined. Objective: We hypothesized that the functional polymorphisms of HMOX1 ((GT) n repeat), CAT (-262C>T-844C>T) and MNSOD-(Ala-9Val) are associated with new onset asthma, and the effects of these variants vary by exposure to ozone, a potent oxidant air pollutant. Method: We assessed this hypothesis in a population-based cohort of non-Hispanic (N=1,125) and Hispanic-White (N=586) children who resided in 12 California communities and who were followed annually for 8 years to ascertain new onset asthma. Measurements: Air pollutants were continuously measured in each of the study communities during the 8 years of study follow-up. Main Result: HMOX1 'short' alleles (< 23 repeats) were associated with a reduced risk for new onset asthma among non-Hispanic Whites (Hazard ratio(HR) 0.64, 95% CI 0.41-0.99). This protective effect was largest in children residing in low-ozone communities (HR 0.48, 95% CI 0.25-0.91) (interaction p-value=0.003). Little evidence for an association with HMOX1 was observed among Hispanic children. In contrast, Hispanic children with a variant of the CAT-262 'T' allele (CT or TT) had an increased risk for asthma (HR 1.78, p-value=0.01). The effects of these polymorphisms were not modified by personal smoking or secondhand-smoke exposure. 4 Conclusions: Functional promoter variants in CAT and HMOX1 showed ethnic-specific associations with new onset asthma. Oxidant gene protection was restricted to children living in low-ozone communities.
2021
Background: Air pollutants induce the increase of inflammatory components in the lungs and the decrease in pulmonary function. Genetic polymorphisms may modify the inflammatory and immunological response to the inhalation of those pollutants. Objective: To investigate effect modification by GST and TNF-α polymorphisms in the association between particulate matter (PM10) and lung function. Methods: This is a cross-sectional epidemiological study with 112 asthmatic children aged 6 to 14 years old. GSTM1, GSTT1, GSTP1, and TNF-α polymorphisms were genotyped using the polymerase chain reaction (PCR) technique. Spirometry tests were conducted. We tested associations using generalized linear models, adjusting for confounding variables. The effect modification of the genetic polymorphisms was assessed, including the genotypes and pollutants. Results: In carriers of the TNF-α-308 GA or AA genotypes, we found a reduction of 11.5% (95% CI: -19.08, -3.30) in FEV1 in the current exposure to PM1...
2008
Background: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesized that GSTP1, GSTM1, exercise and ozone exposure have interrelated effects on asthma pathogenesis. Methods: We examined associations of the well characterized null variant of GSTM1 and four SNPs that characterized common variation in the GSTP1 locus with new-onset asthma in a cohort of 1,610 school children. Children's exercise and ozone-exposure were classified using participation in team sports and community annual average ozone levels, respectively. Results: A two SNP model involving putatively functional variants (rs6591255, rs1695 [Ile105Val]) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (HR 0.60, 95% CI 0.4, 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95%CI 1.1-1.9). Asthma risk increased with level of exercise among ile 105 homo...