title: Mitochondrial genetic background modifies the relationship between traffic-related air pollution exposure and systemic biomarkers of inflammation.
abstract: BACKGROUND
  Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin.
  
  
  OBJECTIVE
  We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations).
  
  
  METHODS
  Inflammation biomarkers were measured weekly in each subject (≤ 12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 µm, 0.25-2.5 µm, and 2.5-10 µm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models.
  
  
  RESULTS
  IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U.
  
  
  CONCLUSIONS
  Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects.
authors.affiliation: Occupational and Environmental Medicine Division, Department of Medicine, School of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Sharine
authors.initials: S
authors.lastname: Wittkopp
authors.forename: Norbert
authors.initials: N
authors.lastname: Staimer
authors.forename: Thomas
authors.initials: T
authors.lastname: Tjoa
authors.forename: Daniel
authors.initials: D
authors.lastname: Gillen
authors.forename: Nancy
authors.initials: N
authors.lastname: Daher
authors.forename: Martin
authors.initials: M
authors.lastname: Shafer
authors.forename: James J
authors.initials: JJ
authors.lastname: Schauer
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Delfino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000397:Air Pollution / Q000032:analysis*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D010084:Oxidation-Reduction; D052638:Particulate Matter / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; C508600:IL6 protein, human; C508603:IL6R protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D019947:Receptors, Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D002097:C-Reactive Protein