Air pollutants, genes and early childhood acute bronchitis

Rakesh Ghosh, Jan Topinka, Jesse P. Joad, Miroslav Dostal, Radim J. Sram, Irva Hertz-Picciotto

Research output: Contribution to journalArticle

8 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume749
Issue number1-2
DOIs
StatePublished - Sep 2013

Fingerprint

Air Pollutants
Tobacco Smoke Pollution
Bronchitis
Tobacco
Polycyclic Aromatic Hydrocarbons
Exons
Cytochrome P-450 CYP1A1
Genes
Logistic Models
Genotype
Aromatic Hydrocarbons
Cotinine
Gene-Environment Interaction
Particulate Matter
Umbilical Cord
Czech Republic
Environmental Exposure
Preschool Children
Xenobiotics
Breast Feeding

Keywords

  • Interaction
  • PAH
  • PM2.5
  • Respiratory illness

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Air pollutants, genes and early childhood acute bronchitis. / Ghosh, Rakesh; Topinka, Jan; Joad, Jesse P.; Dostal, Miroslav; Sram, Radim J.; Hertz-Picciotto, Irva.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 749, No. 1-2, 09.2013, p. 80-86.

Research output: Contribution to journalArticle

Ghosh, Rakesh ; Topinka, Jan ; Joad, Jesse P. ; Dostal, Miroslav ; Sram, Radim J. ; Hertz-Picciotto, Irva. / Air pollutants, genes and early childhood acute bronchitis. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2013 ; Vol. 749, No. 1-2. pp. 80-86.
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