Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study
- PMID: 14726165
- DOI: 10.1016/S0140-6736(03)15262-2
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.
Findings: 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.
Interpretation: GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation.
Comment in
-
Air pollution, oxidative stress, and allergic response.Lancet. 2004 Jan 10;363(9403):95-6. doi: 10.1016/s0140-6736(03)15308-1. Lancet. 2004. PMID: 14726159 No abstract available.
Similar articles
-
Glutathione s-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke.Am J Respir Crit Care Med. 2006 Dec 15;174(12):1335-41. doi: 10.1164/rccm.200509-1424OC. Epub 2006 Oct 5. Am J Respir Crit Care Med. 2006. PMID: 17023730 Free PMC article. Clinical Trial.
-
Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.Thorax. 2016 Jan;71(1):35-44. doi: 10.1136/thoraxjnl-2015-207399. Epub 2015 Nov 16. Thorax. 2016. PMID: 26574583
-
Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled human crossover study.Free Radic Biol Med. 2016 Jul;96:385-91. doi: 10.1016/j.freeradbiomed.2016.04.202. Epub 2016 May 3. Free Radic Biol Med. 2016. PMID: 27151508
-
[Air pollution, asthma and allergy--the importance of different types of particles].Tidsskr Nor Laegeforen. 2002 Aug 10;122(18):1777-82. Tidsskr Nor Laegeforen. 2002. PMID: 12362688 Review. Norwegian.
-
Diesel exhaust as a model xenobiotic in allergic inflammation.Immunopharmacology. 2000 Jul 25;48(3):325-7. doi: 10.1016/s0162-3109(00)00234-4. Immunopharmacology. 2000. PMID: 10960677 Review.
Cited by
-
History of pollutant adjuvants in respiratory allergy.Front Allergy. 2024 Mar 12;5:1374771. doi: 10.3389/falgy.2024.1374771. eCollection 2024. Front Allergy. 2024. PMID: 38533354 Free PMC article. Review.
-
Adjuvant effect of inhaled particulate matter containing free radicals following house-dust mite induction of asthma in mice.Inhal Toxicol. 2023 Dec;35(13-14):333-349. doi: 10.1080/08958378.2023.2289024. Epub 2023 Dec 13. Inhal Toxicol. 2023. PMID: 38060410
-
The role of gene-ambient air pollution interactions in paediatric asthma.Eur Respir Rev. 2022 Nov 15;31(166):220094. doi: 10.1183/16000617.0094-2022. Print 2022 Dec 31. Eur Respir Rev. 2022. PMID: 36384702 Free PMC article. Review.
-
Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers.Inhal Toxicol. 2022;34(11-12):329-339. doi: 10.1080/08958378.2022.2110334. Epub 2022 Aug 15. Inhal Toxicol. 2022. PMID: 35968917 Free PMC article.
-
Transcriptomic and metabolomic associations with exposures to air pollutants among young adults with childhood asthma history.Environ Pollut. 2022 Apr 15;299:118903. doi: 10.1016/j.envpol.2022.118903. Epub 2022 Jan 25. Environ Pollut. 2022. PMID: 35091019 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous