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Title

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

Authors
Imboden, Medea
Brutsche, M.
Schindler, Christian
Downs, S H.
Berger, Wolfgang
Probst-Hensch, Nicole M.
Published in Thorax. 2008, vol. 63, no. 4, p. 322-8
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 > 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.
Keywords AdultAsthma/enzymology/geneticsBronchial Hyperreactivity/enzymology/geneticsBronchoconstrictor Agents/diagnostic useCohort StudiesDisease ProgressionFemaleGenotypeGlutathione Transferase/geneticsHumansMaleMethacholine Chloride/diagnostic usePolymorphism, Single Nucleotide/geneticsProspective StudiesRisk Factors
Identifiers
PMID: 18057098
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Article (Author postprint) (322 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://thorax.bmj.com/cgi/content/full/63/4/322
Structures
Research groups SAPALDIA Team
Pneumologie Clinique (576)
L'épithélium respiratoire (852)
Monitoring du programme d'études et de formation pré-graduée de médecine (877)
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(ISO format)
IMBODEN, Medea et al. Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults. In: Thorax, 2008, vol. 63, n° 4, p. 322-8. https://archive-ouverte.unige.ch/unige:2071

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Deposited on : 2009-06-17

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