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

Curjuric, I. and Imboden, M. and Schindler, C. and Downs, S. H. and Hersberger, M. and Liu, L. J. and Matyas, G. and Russi, E. W. and Schwartz, J. and Thun, G. A. and Postma, D. S. and Rochat, T. and Probst-Hensch N. M., . (2010) HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction. The European respiratory journal, 35 (3). pp. 505-514.

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Official URL: http://edoc.unibas.ch/dok/A5842909

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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
Faculties and Departments:03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Biostatistics > Biostatistics - Frequency Modelling (Schindler)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Environmental Exposures (Liu)
UniBasel Contributors:Schindler, Christian and Curjuric, Ivan and Liu, Lee-Jane S. and Probst Hensch, Nicole
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Munksgaard
ISSN:0903-1936
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Nov 2017 09:46
Deposited On:24 May 2013 09:10

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