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Decreased PM10 exposure attenuates age-related lung function decline : genetic variants in p53, p21, and CCND1 modify this effect

Imboden, Medea and Schwartz, Joel and Schindler, Christian and Curjuric, Ivan and Berger, Wolfgang and Liu, Sally L. J. and Russi, Erich W. and Ackermann-Liebrich, Ursula and Rochat, Thierry and Probst-Hensch, Nicole M.. (2009) Decreased PM10 exposure attenuates age-related lung function decline : genetic variants in p53, p21, and CCND1 modify this effect. Environmental Health Perspectives, 117 (9). pp. 1420-1427.

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Official URL: http://edoc.unibas.ch/dok/A5843182

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Abstract

BACKGROUND: Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. OBJECTIVE: We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75)) associated with improved air quality. METHODS: Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter > or = 10 microm (PM(10)) to each participant's residential history 12 months before the baseline and follow-up assessments. RESULTS: The effect of diminishing PM(10) exposure on FEF(25-75) decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-microg/m(3) decline in average PM(10) exposure over an 11-year period attenuated the average annual decline in FEF(25-75) by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes, and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. CONCLUSIONS: Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Air Pollution and Health (Künzli)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Air Pollution and Health (Künzli)
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) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health > Physical Hazards and Health (Röösli)
UniBasel Contributors:Liu, Lee-Jane S. and Schindler, Christian and Curjuric, Ivan and Ackermann-Liebrich, Ursula A. and Probst Hensch, Nicole
Item Type:Article, refereed
Publisher:National Institute of Environmental Health Sciences
ISSN:0091-6765
e-ISSN:1552-9924
Note:Publication type according to Uni Basel Research Database: Journal article -- Reproduced with permission from Environmental Health Perspectives
Language:English
Identification Number:
Last Modified:31 Aug 2017 09:41
Deposited On:11 Oct 2012 15:27

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