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


Imboden, M; Rochat, T; Brutsche, M; Schindler, C; Downs, S H; Gerbase, M W; Berger, W; Probst-Hensch, N M (2008). Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults. Thorax, 63(4):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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > Institute of Medical Molecular Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
540 Chemistry
Language:English
Date:2008
Deposited On:24 Feb 2009 13:16
Last Modified:05 Apr 2016 12:33
Publisher:BMJ Publishing Group
ISSN:0040-6376
Publisher DOI:10.1136/thx.2007.085555
PubMed ID:18057098
Permanent URL: http://doi.org/10.5167/uzh-5216

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