细颗粒物（PM10）暴露减少可减轻与年龄相关的肺功能下降：p53、p21和细胞周期蛋白D1（CCND1）中的基因变异可改变这种效应。
Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.
作者信息
Imboden Medea, Schwartz Joel, Schindler Christian, Curjuric Ivan, Berger Wolfgang, Liu Sally L J, Russi Erich W, Ackermann-Liebrich Ursula, Rochat Thierry, Probst-Hensch Nicole M
机构信息
Department of Chronic Disease Epidemiology, Institute of Social and Preventive Medicine, University of Zurich, Sumatrastrasse 30, Zurich, Switzerland.
出版信息
Environ Health Perspect. 2009 Sep;117(9):1420-7. doi: 10.1289/ehp.0800430. Epub 2009 May 26.
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.
背景
此前有研究表明，减少空气中颗粒物的暴露与肺功能随年龄增长的下降减缓有关。然而，空气质量改善带来的益处是否取决于遗传背景尚不清楚。最近的证据表明，基因p53、p21以及细胞周期控制基因细胞周期蛋白D1（CCND1）参与了支气管细胞对空气污染的反应。
目的
在瑞士成人空气污染与心肺疾病队列研究（SAPALDIA）的4326名参与者中，我们确定了三个基因[CCND1（rs9344 [P242P]，rs667515）、p53（rs1042522 [R72P]）和p21（rs1801270 [S31R]）]中的四个单核苷酸多态性是否改变了之前观察到的与空气质量改善相关的用力肺活量25%至75%之间用力呼气流量（FEF(25 - 75)）下降的减缓情况。
方法
基于人群的前瞻性SAPALDIA队列研究中的受试者于1991年和2002年通过肺活量测定、问卷调查以及采集生物样本进行基因分型评估。我们将空气动力学直径≤10微米的颗粒物（PM(10)）的空间分辨浓度分配给每位参与者在基线和随访评估前12个月的居住史。
结果
p53 R72P、CCND1 P242P和CCND1 rs667515似乎改变了PM(10)暴露减少对FEF(至75)下降的影响。例如，在11年期间平均PM(10)暴露每下降10微克/立方米，CCND1（P242P）GG基因型纯合子参与者的FEF(25 - 75)平均每年下降减缓21.33毫升/年（95%置信区间，10.57 - 32.08），GA基因型参与者为13.72毫升/年（5.38 - 22.06），AA基因型参与者为6.00毫升/年（-4.54至16.54）。
结论
我们的结果表明，细胞周期控制基因可能会改变空气质量改善对成年人呼吸功能有益的程度。
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