title: Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study.
abstract: BACKGROUND
  Particulate pollution is associated with the occurrence of asthma and allergy. The model pollutant, diesel exhaust particles, can participate with allergens in starting and exacerbating allergic airway diseases in part by production of reactive oxygen species. Glutathione-S-transferases (GSTs) can metabolise reactive oxygen species and detoxify xenobiotics present in diesel exhaust particles. We tested the hypothesis that null genotypes for GSTM1 and GSTT1, and GSTP1 codon 105 variants (I105 and V105) are key regulators of the adjuvant effects of diesel exhaust particles on allergic responses.
  
  
  METHODS
  Patients sensitive to the ragweed allergen were challenged intranasally with allergen alone and with allergen plus diesel exhaust particles in a randomised order at separate visits. Nasal allergen-specific IgE, histamine, interleukin 4, and interferon gamma concentrations were measured before and 24 h after challenge.
  
  
  RESULTS
  Individuals with GSTM1 null or the GSTP1 I105 wildtype genotypes showed enhanced nasal allergic responses in the presence of diesel exhaust particles. Compared with patients with a functional GSTM1 genotype, GSTM1 null patients had a significantly larger increase in IgE (median 102.5 U/mL [range 1.0-510.5] vs 45.5 U/mL [1.5-60.6], p=0.03) and histamine (14.0 nmol/L [-0.2-24.7] vs 7.4 nmol/L [1.2-12.3], p=0.02) after diesel exhaust particles plus allergen challenge. The I105 GSTP1 genotype was associated with an increase in IgE (120.3 U/mL [6.7-510.5] vs 27.7 U/mL [-1.5-60.6], p=0.03) and histamine (13.8 nmol/L [3.1-24.7] vs 5.2 nmol/L [-0.2-19.6], p=0.01) after challenge with diesel exhaust particles and allergens. The diesel exhaust particles enhancement was largest in patients with both the GSTM1 null and GSTP1 I/I genotypes.
  
  
  CONCLUSIONS
  GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA. gillilan@usc.edu
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Li
authors.forename: Andrew
authors.initials: A
authors.lastname: Saxon
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
mesh_terms: D000388:Air; D000485:Allergens / Q000276:immunology; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008297:Male; D009299:Nasal Provocation Tests / Q000379:methods; D010919:Placebos; D017382:Reactive Oxygen Species / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology; D001335:Vehicle Emissions / Q000009:adverse effects; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D000485:Allergens; D010919:Placebos; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D015262:Xenobiotics; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase