Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

Objective. Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. Material and methods. Serum selenium concentration was measured, GPX1 polymorphisms were genotyped and smoking history was obtained in a Danish population-derived case-base cohort of 1,191 subjects designed to evaluate risk factors for asthma. GPX1 activity was measured in 134 male and 164 female subjects equally distributed according to genotype of GPX1. Among these subjects, 82 (28 %) had doctor-diagnosed asthma. Results. The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p0.001). In men, activity was positively associated with serum selenium concentration (p=0.005) and negatively associated with both active smoking (p=0.009) and exposure to environmental tobacco smoke (p=0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild-type, the heterozygote and the homozygote variant type, respectively (p=0.001). Doctor-diagnosed asthma was unrelated to GPX1 activity in either sex. Conclusion. Determinants for activity in the oxidative enzyme GPX1 show marked differences between the sexes, but the activity is not associated with asthma. Sex ought to be taken into consideration when analysing the activity of the enzyme.