title: The effect of oxidative stress polymorphisms on the association between long-term black carbon exposure and lung function among elderly men.
abstract: BACKGROUND
  Black carbon (BC) is a pro-oxidant, traffic-related pollutant linked with lung function decline. We evaluated the influence of genetic variation in the oxidative stress pathway on the association between long-term BC exposure and lung function decline.
  
  
  METHODS
  Lung function parameters (FVC and FEV1) were measured during one or more study visits between 1995 and 2011 (n=651 participants) among an elderly cohort: the Normative Aging Study. Residential BC exposure levels were estimated using a spatiotemporal land use regression model. We evaluated whether oxidative stress variants, combined into a genetic score, modify the association between 1-year and 5-year moving averages of BC exposure and lung function levels and rates of decline, using linear mixed models.
  
  
  RESULTS
  We report stronger associations between long-term BC exposure and increased rate of lung function decline, but not baseline lung function level, among participants with higher oxidative stress allelic risk profiles compared with participants with lower risk profiles. Associations were strongest when evaluating 5-year moving averages of BC exposure. A 0.5 µg/m(3) increase in 5-year BC exposure was associated with a 0.1% yearly increase in FVC (95% CI -0.5 to 0.7) among participants with low genetic risk scores and a 1.3% yearly decrease (95% CI -1.8 to -0.8) among those with high scores (p-interaction=0.0003).
  
  
  CONCLUSIONS
  Our results suggest that elderly men with high oxidative stress genetic scores may be more susceptible to the effects of BC on lung function decline. The results, if confirmed, should inform air-quality recommendations in light of a potentially susceptible subgroup.
authors.affiliation: Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Mordukhovich
authors.affiliation: Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA INSERM, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France University of Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France CHU de Grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D002374:Catalase / Q000235:genetics; D005541:Forced Expiratory Volume / Q000235:genetics*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D053260:Soot / Q000633:toxicity*; D013997:Time Factors; D014797:Vital Capacity / Q000235:genetics*
chemical_list: D002374:Catalase; D005721:Glutamate-Cysteine Ligase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); D053260:Soot; C496541:HMOX1 protein, human; C447479:NQO1 protein, human; C496556:GSTP1 protein, human; C546365:GCLM protein, human
keywords: COPD epidemiology; COPD ÀÜ Mechanisms; Clinical Epidemiology; Oxidative Stress