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HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

2009; European Respiratory Society; Volume: 35; Issue: 3 Linguagem: Inglês

10.1183/09031936.000443-2009

1399-3003

I. Curjuric, M. Imboden, Christian Schindler, S. H. Downs, M. Hersberger, S. L. J. Liu, G. Matyas, Erich W. Russi, Joel Schwartz, Gian Andri Thun, Dirkje S. Postma, Thierry Rochat, Nicole Probst‐Hensch,

Renal and related cancers

Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM 10 ) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S -transferase ( GST ) and haem oxygenase-1 ( HMOX1 ) genes, important for oxidative stress defence, modify these beneficial effects. A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM 10 exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25–75% of forced vital capacity (FEF 25–75% ) and interactions with PM 10 reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT) n promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.Ile105Val, using mixed linear regression models. HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM 10 reduction were detected: a 10 μg·m −3 reduction significantly attenuated annual FEF 25–75% decline by 15.3 mL·s −1 only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT) n promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 μg·m −3 reduction (26.5 mL·s −1 and 27.3 mL·s −1 respectively) than non-carriers. Benefits of a reduction in PM 10 exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.