title: Air pollutants, genes and early childhood acute bronchitis.
abstract: BACKGROUND
  Studies have reported gene-by-environment interaction for chronic respiratory conditions but none on acute illnesses in children. We investigated, longitudinally, whether genotype modifies the relationship of environmental exposures (second-hand tobacco smoke, polycyclic aromatic hydrocarbons, particulate matter <2.5μm (PM2.5)) with acute bronchitis in children below two years.
  
  
  METHODS
  A random sample of 1133 children, born between 1994 and 1998, in two districts of the Czech Republic, was followed-up from birth, of which 793 were genotyped. Pediatric records were abstracted for respiratory illnesses. Second-hand tobacco smoke exposure from household members was obtained through questionnaires and verified using urine cotinine. Air monitoring provided estimates of ambient polycyclic aromatic hydrocarbons and PM2.5. Additionally, we collected information on a range of potential confounders including breastfeeding history, indoor fuel use, other children in household, maternal characteristics, ambient temperature etc. DNA was extracted from tissues taken from the middle of the placenta, opposite the umbilical cord. We examined six single nucleotide polymorphisms (GSTM1, GSTP1, GSTT1, CYP1A1 MspI, EPHX1 exon 3 and 4) and one (EPHX1) diplotype. To investigate effect measure modification we constructed logistic regression models using generalized estimating equations (for repeated observations) stratified by genotypes.
  
  
  RESULTS
  The EPHX1 low activity diplotype consistently imparts greater susceptibility to bronchitis from second-hand tobacco smoke, polyclic aromatic hydrocarbons (PAH) and PM2.5. Each of these three classes of exposure also showed elevated risk for bronchitis in the presence of either one or two histidines at exon 3 and exon 4 of EPHX1. Additional effect modifiers include CYP1A1 and GSTT1.
  
  
  CONCLUSIONS
  Several xenobiotic metabolizing genes may modify the impact of second-hand tobacco smoke and ambient air pollutants, polycyclic aromatic hydrocarbons and PM2.5, on acute bronchitis in preschool children.
authors: Department of Public Health Sciences, University of California, Davis, USA. Electronic address: rakesh.ghosh@gmail.com.
authors: Rakesh
authors: R
authors: Ghosh
authors: Jan
authors: J
authors: Topinka
authors: Jesse P
authors: JP
authors: Joad
authors: Miroslav
authors: M
authors: Dostal
authors: Radim J
authors: RJ
authors: Sram
authors: Irva
authors: I
authors: Hertz-Picciotto
mesh_terms: D000208:Acute Disease; D000328:Adult; D017668:Age of Onset; D000393:Air Pollutants / Q000009:adverse effects*; D001991:Bronchitis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D002675:Child, Preschool; D015331:Cohort Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496556:GSTP1 protein, human; C522330:EPHX1 protein, human
keywords: COPD; CYP1A1; EPHX1; GST; GWAS; HWE; Hardy–Weinberg equilibrium; Interaction; PAH; PM2.5; Respiratory illness; SHS; chronic obstructive pulmonary disease; cytochrome P450 MspI; epoxide hydrolases; genome wide association studies; glutathione S-transferases; polycyclic aromatic hydrocarbons; second hand smoke