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Asthma
Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults
  1. M Imboden1,2,
  2. T Rochat3,
  3. M Brutsche4,
  4. C Schindler5,
  5. S H Downs5,
  6. M W Gerbase3,
  7. W Berger2,
  8. N M Probst-Hensch1,
  9. the SAPALDIA Team
  1. 1
    Institutes of Social and Preventive Medicine and Surgical Pathology, Cancer Registry/Molecular Epidemiology, University of Zurich, Zurich, Switzerland
  2. 2
    Institute of Medical Genetics, University of Zurich, Zurich, Switzerland
  3. 3
    Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland
  4. 4
    Pneumology, University Hospital of Basel, Basel, Switzerland
  5. 5
    Institute of Social and Preventive Medicine, University of Basel, Basel, Switzerland
  1. Dr N M Probst-Hensch, Institute of Social and Preventive Medicine, Molecular Epidemiology/Cancer Registry, University of Zürich, Vogelsangstrasse 10, CH-8091 Zürich, Switzerland; nicole.probst{at}usz.ch

Abstract

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 ⩾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.

https://doi.org/10.1136/thx.2007.085555

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    Footnotes

    • Funding: This research has been supported by the Swiss National Science Foundation (grants no 4026-28099, 3347CO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 32-65896.01, 32-59302.99, 32-52720.97, 32-4253.94), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton’s government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Zurich, the Swiss Lung League, the canton’s Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticino and Zurich and Freiwillige Akademische Gesellschaft, Basel.

    • Competing interests: None.

    • Ethics approval: Ethical approval for the study was given by the central ethics committee of the Swiss Academy of Medical Sciences and the Cantonal ethics committees for each of the eight examination areas.

    • Local field workers: Aarau: M Broglie, M Bünter, D Gashi; Basel: R Armbruster, T Damm, U Egermann, M Gut, L Maier, A Vögelin, L Walter; Davos: D Jud, N Lutz; Geneva: M Ares, M Bennour, B Galobardes, E Namer; Lugano: B Baumberger, S Boccia Soldati, E Gehrig-Van Essen, S Ronchetto; Montana: C Bonvin, C Burrus; Payerne: S Blanc, AV Ebinger, M L Fragnière, J Jordan; Wald: R Gimmi, N Kourkoulos, U Schafroth. Administrative staff: N Bauer, D Baehler, C Gabriel, R Nilly.

      SAPALDIA Team: Study directorate: T Rochat (p), U Ackermann-Liebrich (e), J M Gaspoz (c), P Leuenberger (p), LJS Liu (exp), NM Probst Hensch (e/g), C Schindler (s). Scientific team: J C Barthélémy (c), W Berger (g), R Bettschart (p), A Bircher (a), G Bolognini (p), O Brändli (p), M Brutsche (p), L Burdet (p), M Frey (p), MW Gerbase (p), D Gold (e/c/p), W Karrer (p), R Keller (p), B Knöpfli (p), N Künzli (e/exp), U Neu (exp), L Nicod (p), M Pons (p), E Russi (p), P Schmid-Grendelmeyer (a), J Schwartz (e), P Straehl (exp), JM Tschopp (p), A von Eckardstein (cc), J P Zellweger (p), E Zemp Stutz (e). Scientific team at coordinating centres: P O Bridevaux (p), I Curjuric (e), S H Downs (e/s), D Felber Dietrich (c), A Gemperli (s), D Keidel (s), M Imboden (g), P Staedele-Kessler (s), G A Thun (g). [(a) allergology, (c) cardiology, (cc) clinical chemistry, (e) epidemiology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (p) pneumology, (s) statistics].