Genetic polymorphisms in antioxidative enzymes are associated to FEV(1) in smokers independently of asthma

Tine Birgitte Halsen Malling, Torben Sigsgaard, Charlotte Brasch Andersen, Lone Frischknecht, Helle Raun Andersen, Torben A Kruse, David Sherson, Lars Rauff Skadhauge, Gert Thomsen, Jesper Baelum, Oyvind Omland

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In this study, we hypothesized that the genotypes coding for low antioxidative enzyme activity are associated with asthma and reduced lung function. Using the ECRHS protocol, we enlisted 1,091 Danish subjects in this cross-sectional study. Asthma phenotypes were defined as asthma symptoms in combination with steroid usage, bronchial hyperresponsiveness, and atopy. These phenotypes and lung function were analysed with respect to Glutathione peroxidase, GPX1 (Pro198Leu, rs1050450), Manganese Superoxide dismutase, SOD2 (Ala16Val, rs4880) and three Glutathione S-transferases; GSTP1 (Ile105Val, rs1695), GSTT1 (gene copy number), and GSTM1 (gene copy number). We found no associations between these genotypes and the asthma phenotypes. For the 201 subjects identified as current smokers and recruited via random sampling, an association was seen between increasing number of genotypes coding for high antioxidative enzyme activity (GPX1 Pro/Pro, SOD2 Val/Val, GSTP1 Ile/Ile, GSTT1 two copies, GSTM1 two copies) and FEV(1) % predicted. The increase in FEV(1) % predicted was 2.0% (95% CI; 0.3-3.8) per genotype. There was no identified significance for the inverse association between FEV(1) % predicted and number of genotypes coding for low antioxidative enzyme activity. The present study does not support the hypothesis that asthma is associated with genotypes of these major antioxidative enzymes. However, we speculate that since we see an impact of these genotypes on lung function in young adult smokers, polymorphisms in antioxidative enzymes may contribute to the range of susceptibility of smokers have to COPD.
TidsskriftClinical Respiratory Journal
Udgave nummer1
Sider (fra-til)46-55
StatusUdgivet - 2012