Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.
Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.
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DOI：
10.1289/ehp.0800430
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发表时间：
2009-09
影响因子：
10.4
通讯作者：
SAPALDIA Team
中科院分区：
文献类型：
--
作者：
Imboden M;Schwartz J;Schindler C;Curjuric I;Berger W;Liu SL;Russi EW;Ackermann-Liebrich U;Rochat T;Probst-Hensch NM;SAPALDIA Team
以前，减少空气中颗粒物的暴露与减少与年龄相关的肺功能衰退有关。然而，空气质量改善带来的好处是否取决于遗传背景尚不清楚。最近的证据表明，基因p53和p21以及细胞周期控制基因cyclin D1 （CCND1）参与了支气管细胞对空气污染的反应。在瑞士空气污染与成人心肺疾病队列研究（SAPALDIA）的4326名参与者中，我们确定了三个基因中的四个单核苷酸多态性[CCND1 (rs9344 [P242P], rs667515), p53 （rs1042522 [R72P]）和p21 (rs1801270 [S31R])]是否改变了先前观察到的与空气质量改善相关的强制呼气流量下降的衰减，该衰减在强制肺气量（FEF25-75）的25%至75%之间。前瞻性基于人群的SAPALDIA队列研究对象于1991年和2002年通过肺活量测定法、问卷调查和生物样本收集进行基因分型评估。在基线和随访评估前12个月，我们将空气动力学直径≤10 μm的颗粒物（PM10）的空间分辨浓度分配给每位参与者的居住史。PM10暴露减少对FEF25-75下降的影响似乎被p53 R72P、CCND1 P242P和CCND1 rs667515所修饰。例如，在11年期间，平均PM10暴露量下降10 μg/m3，使CCND1 (P242P) GG基因型参与者的FEF25-75年平均下降21.33 mL/年（95%置信区间为10.57-32.08），GA基因型参与者的FEF25-75年平均下降13.72 mL/年（5.38-22.06），AA基因型参与者的FEF25-75年平均下降6.00 mL/年（- 4.54 - 16.54）。我们的研究结果表明，细胞周期控制基因可能会改变空气质量改善对成人呼吸功能有益的程度。
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. 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. 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. 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 aver-age 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. Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.
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DOI：
10.1007/s00038-005-4075-5
发表时间：
2005-01-01
期刊：
SOZIAL-UND PRAVENTIVMEDIZIN
影响因子：
--
作者：
Ackermann-Liebrich, U;Kuna-Dibbert, B;Leuenberger, P
通讯作者：
Leuenberger, P
DOI：
10.1164/ajrccm.155.1.9001300
发表时间：
1997-01-01
影响因子：
24.7
作者：
AckermannLiebrich, U;Leuenberger, P;Zemp, E
通讯作者：
Zemp, E
影响因子：
3.5
作者：
Choi, Yi Young;Kang, Hyo-Kyung;Park, Jae Yong
通讯作者：
Park, Jae Yong
影响因子：
30.8
作者：
Bergamaschi, Daniele;Samuels, Yardena;Lu, Xin
通讯作者：
Lu, Xin
影响因子：
24.3
作者：
KUNZLI, N;ACKERMANNLIEBRICH, U;ZEMP, E
通讯作者：
ZEMP, E