Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma.

Abstract

In this study, we hypothesised that the genotypes coding for low antioxidative enzyme activity are associated with asthma and reduced lung function. Using the European Community Respiratory Health Survey protocol, we enlisted 1091 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 forced expiratory volume in 1 s (FEV1%) predicted. The increase in FEV1% predicted was 2.0% (95% confidence interval 0.3-3.8) per genotype. There was no identified significance for the inverse association between FEV1% 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 Chronic obstructive lung disease.