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HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1192685
Author(s) Curjuric, I.; Imboden, M.; Schindler, C.; Downs, S. H.; Hersberger, M.; Liu, L. J.; Matyas, G.; Russi, E. W.; Schwartz, J.; Thun, G. A.; Postma, D. S.; Rochat, T.; Probst-Hensch N. M.,
Author(s) at UniBasel Probst Hensch, Nicole
Schindler, Christian
Curjuric, Ivan
Liu, Lee-Jane S.
Year 2010
Title HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction
Journal The European respiratory journal
Volume 35
Number 3
Pages / Article-Number 505-14
Keywords Exposure to particles with a 50% cut-off aerodynamic diameter of 10 mu m, forced expiratory flow at 25-75% of forced vital capacity, general population sample, glutathione S-transferase, haem oxygenase-1, lung function decline
Abstract Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 microm (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 microg.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 microg.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
Publisher Munksgaard
ISSN/ISBN 0903-1936
Full Text on edoc No
Digital Object Identifier DOI 10.1183/09031936.00044309
PubMed ID
ISI-Number WOS:000275239000009
Document type (ISI) Journal Article

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