title: Air pollution and childhood bronchitis: Interaction with xenobiotic, immune regulatory and DNA repair genes.
abstract: BACKGROUND
  Gene-environment interactions have been investigated for diseases such as asthma, chronic obstructive pulmonary disease, cancer etc. but acute disease like bronchitis has rarely been studied. We investigated interactions between air pollution (polycyclic aromatic hydrocarbons (PAH) and particulate matter <2.5 μm (PM2.5)) and single nucleotide polymorphisms (SNP) in EPHX1, IL10, STAT4 and XPC genes in relation to bronchitis in children aged 0-2 years.
  
  
  METHODS
  A stratified random sample of 1133 Czech children, born between 1994 and 1998 in two districts, were followed since birth, of which 626 were genotyped. Pediatrician-diagnosed bronchitis episodes were obtained from the medical records. Central-site monitors measured air pollution exposure. We used multivariable logistic regression and estimated coefficients using generalized estimating equations. Interaction was assessed between pollutants and genes and associations in genotype-specific strata were presented. False discovery rate was used to adjust for multiple comparisons.
  
  
  RESULTS
  There were 803 episodes of bronchitis with an incidence rate of 56 per 1000 child-months. We found significant gene-environment interaction between PAH and four SNPs (EPHX1, (rs2854461), STAT4 (rs16833215), XPC (rs2228001 and rs2733532)), which became non-significant after adjusting for multiple comparisons. PM2.5 interactions with two XPC SNPs (rs2228001 and rs2733532) remained significant after accounting for multiple comparisons and those with CC alleles had a more than doubling of odds, OR=2.65 (95% CI: 1.91, 3.69) and 2.72 (95% CI: 1.95, 3.78), respectively, per 25 μg/m(3) increase in exposure.
  
  
  CONCLUSIONS
  The findings suggest that the DNA repair gene XPC may play an important role in the air pollution-induced pathogenesis of the inflammatory disease bronchitis.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States. Electronic address: rakesh.ghosh@gmail.com.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Honkova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dostal
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
authors.affiliation: Department of Public Health Sciences, University of California, Davis, United States.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
mesh_terms: D000293:Adolescent; D000393:Air Pollutants / Q000009:adverse effects / Q000032:analysis*; D001249:Asthma / Q000453:epidemiology; D001991:Bronchitis / Q000453:epidemiology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018153:Czech Republic; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015994:Incidence; D008297:Male; D052638:Particulate Matter / Q000009:adverse effects / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D015262:Xenobiotics / Q000009:adverse effects / Q000032:analysis*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D015262:Xenobiotics