Academic journal article Environmental Health Perspectives

Decreased [PM.Sub.10] Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in P53, P21, and CCND1 Modify This Effect

Academic journal article Environmental Health Perspectives

Decreased [PM.Sub.10] Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in P53, P21, and CCND1 Modify This Effect

Article excerpt

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 Dl (CCNDI) 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 [CCNDI (rs9344 [P242P], rs667515), p53 (rsl042522 [R72P]), and p21 (rsl801270 [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 paniculate matter with aerodynamic diameter < 10 [mu]m ([PM.sub.10]) to each participant's residential history 12 months before the baseline and follow-up assessments.

RESULTS: The effect of diminishing [PM.sub.10] exposure on [FEF.sub.(25-75)] decline appeared to be modified by p53 R72P, CCNDI P242P, and CCNDI rs667515. For example, a 10-[[mu]g/[m.sup.3]] decline in average [PM.sub.10] exposure over an 11-year period attenuated the average annual decline in [FEF.sub.(25-75)] by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCNDI (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]

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A large body of evidence underscores the adverse effect of long-term exposure to ambient particulate matter (PM) air pollution on respiratory health (Brunekreef and Forsberg 2005; Gotschi et al. 2008). Among adults in Switzerland, we have previously demonstrated cross-sectionally that residents of more polluted areas have lower lung function (Ackermann-Liebrich et al. 1997). More recently, we presented evidence from the same population-based cohort [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA)] that decreasing exposure to airborne PM attenuated the average age-related decline in lung function. The associations were strongest for respiratory function tests reflecting small-airway function, namely, [FEF.sub.25-75] [forced expiratory flow between 25% and 75% of forced vital capacity (FVC)] (Downs et al. 2007). Similar results from studies following interventions such as building bypasses for congested traffic routes (Burr et al. 2004; Hedley et al. 2002) or banning environmental tobacco smoke (ETS) exposure (Goodman et al. 2007; Menzies et al. 2006) showed that the improvements in air quality were accompanied by a decrease in cardiopulmonary mortality and an improvement in respiratory symptoms and lung function. However, it is still unknown whether all subjects benefit equally from a reduction in air pollution.

Variation in genes mediating the pathobiological effect of air pollution in the lung may codetermine the degree to which a person benefits from better air quality. Experimental evidence indicates that PM alters expression of tumor protein gene p53, cyclin-dependent kinase inhibitor 1A gene (p21), and the cyclin Dl gene (CCNDl) and subsequently affects cell proliferation and apoptosis of lung fibroblasts, lymphocytes, and alveolar epithelial cells (Bayram et al. …

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