Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults

Imboden, M. and Rochat, T. and Brutsche, M. and Schindler, C. and Downs, S. H. and Gerbase, M. W. and Berger, W. and Probst-Hensch, N. M. and Sapaldia, Team. (2008) Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults. Thorax, Vol. 63. pp. 322-328.

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Official URL: http://edoc.unibas.ch/dok/A6004228

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BACKGROUND: Bronchial hyperresponsiveness (BHR) and variation in glutathione S-transferase (GST) genes have been associated with asthma risk. The relationship of these two risk factors with adult onset asthma in the general population was investigated. METHODS: GSTP1 Ile105Val single nucleotide polymorphism and GSTM1 and GSTT1 gene deletion polymorphisms were genotyped in the population-representative SAPALDIA cohort. BHR was assessed at baseline by methacholine challenge and defined as a fall of < or =20% in forced expiratory volume in 1 s. Independent effects of GST polymorphisms and BHR on new onset of asthma after 11 years of follow-up were estimated by multiple logistic regression analysis, adjusting for relevant baseline measures. Effect modification was assessed by including interaction terms in the model. RESULTS: Among 4426 asthma-free participants at baseline, 14% had BHR. At follow-up, 3.3% reported new onset of physician-diagnosed asthma. BHR (p>0.001) and GSTP1 Ile105Val genotype (p = 0.005) were independently associated with incident asthma, but no association was seen for GSTT1 and GSTM1 gene deletion polymorphisms. Among subjects free of respiratory symptoms at baseline, the effect of BHR on the risk of physician-diagnosed asthma at follow-up was restricted to GSTP1 105 Ile/Ile carriers (OR 4.57, 95% CI 2.43 to 8.57 vs 1.40, 95% CI 0.58 to 3.39; p for interaction = 0.023). CONCLUSIONS: If confirmed by independent studies, our results suggest that GSTP1 Ile105Val genotype strongly determines the progression of BHR to physician-diagnosed asthma in the general population.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health > Physical Hazards and Health (Röösli)
UniBasel Contributors:Schindler, Christian and Brutsche, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:British Medical Association
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:08
Deposited On:11 Oct 2012 15:27

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