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Glutathione-S transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults
  1. Medea Imboden (imboden{at}medgen.unizh.ch)
  1. University of Zurich, Switzerland
    1. Thierry Rochat (thierry.rochat{at}hcuge.ch)
    1. University Hospitals of Geneva, Switzerland
      1. Martin H Brutsche (mbrutsche{at}uhbs.ch)
      1. University Hospital of Basel, Switzerland
        1. Christian Schindler (christian.schindler{at}unibas.ch)
        1. University of Basel, Switzerland
          1. Sara H Downs (s.downs{at}unibas.ch)
          1. University of Basel, Switzerland
            1. Margaret W Gerbase (margaret.gerbase{at}hcuge.ch)
            1. University of Geneva School of Medicine, Switzerland
              1. Wolfgang Berger (berger{at}medgen.unizh.ch)
              1. University of Zurich, Switzerland
                1. Nicole M Probst-Hensch (nicole.probst{at}usz.ch)
                1. University of Zurich, Switzerland
                  1. the SAPALDIA Team (nicole.probst{at}usz.ch)
                  1. University of Zurich, Switzerland

                    Abstract

                    Background: Bronchial hyper-responsiveness (BHR) and variation in Glutathione S-transferase (GST) genes have been associated with asthma risk. We investigated the relationship of these two risk factors on adult onset asthma in the general population.

                    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 ≥ 20% drop in forced expiratory volume in one second. Independent effects of GST polymorphisms and BHR on new onset of asthma after eleven 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 (odds ratio (OR): 4.57 (95% Confidence Interval: 2.43 - 8.57) vs. 1.40 (0.58 - 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.

                    • Asthma
                    • Bronchial Hyperreactivity
                    • Cohort Study
                    • Incidence
                    • Polymorphism

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