Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-23387
Imboden, M; Schwartz, J; Schindler, C; Curjuric, I; Berger, W; Liu, S L; Russi, E W; Ackermann-Liebrich, U; Rochat, T; Probst-Hensch, N M (2009). Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect. Environ Health Perspect, 117(9):1420-1427.
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 (FEF25–75) 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 ≤ 10 μm (PM10) to each participant’s residential history 12 months before the baseline and follow-up assessments.
Results: The effect of diminishing PM10 exposure on FEF25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in average PM10 exposure over an 11-year period attenuated the average annual decline in FEF25–75 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.
Key words: air pollution, cell cycle, cohort study, genes, respiratory function tests. Environ Health Perspect 117:1420–1427 (2009). doi:10.1289/ehp.0800430 available via http://dx.doi.org/ [Online 26 May 2009]
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry|
04 Faculty of Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Institute of Medical Molecular Genetics
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||28 Oct 2009 13:32|
|Last Modified:||28 Nov 2013 01:47|
|Publisher:||National Institute of Environmental Health Sciences|
|Additional Information:||Free full text article in PubMed|
|Citations:||Web of Science®. Times Cited: 9|
Scopus®. Citation Count: 9
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