英国生物库中的环境空气污染、遗传风险与端粒长度。
Ambient air pollution, genetic risk and telomere length in UK biobank.
机构信息
Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, 430030, Wuhan, China.
Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, 430030, Wuhan, China.
出版信息
J Expo Sci Environ Epidemiol. 2024 Sep;34(5):845-852. doi: 10.1038/s41370-023-00587-1. Epub 2023 Aug 7.
BACKGROUND
Telomere length (TL) is a biomarker of genomic aging. The evidence on the association between TL and air pollution was inconsistent. Besides, the modification effect of genetic susceptibility on the air pollution-TL association remains unknown.
OBJECTIVE
We aimed to evaluate the association of ambient air pollution with TL and further assess the modification effect of genetic susceptibility.
METHODS
433,535 participants with complete data of TL and air pollutants in UK Biobank were included. Annual average exposure of NO, NO, PM and PM was estimated by applying land use regression models. Genetic risk score (GRS) was constructed using reported telomere-related SNPs. Leukocyte TL was measured by quantitative polymerase chain reaction (qPCR). Multivariable linear regression models were employed to conduct associational analyses.
RESULTS
Categorical exposure models and RCS models both indicated U-shaped (for NO and NO) and L-shaped (for PM and PM) correlations between air pollution and TL. In comparison to the lowest quartile, the 2nd and 3rd quartile of NO (q2: -1.3% [-2.1%, -0.4%]; q3: -1.2% [-2.0%, -0.3%], NO (q2: -1.3% [-2.1%, -0.5%]; q3: -1.4% [-2.2%, -0.5%]), PM (q2: -0.8% [-1.7%, 0.0%]; q3: -1.3% [-2.2%, -0.5%]), and the third quartile of PM (q3: -1.1% [-1.9%, -0.2%]) were inversely associated with TL. The highest quartile of NO was positively correlated with TL (q4: 1.0% [0.0%, 2.0%]), whereas the negative correlation between the highest quartile of other pollutants and TL was also attenuated and no longer significant. In the genetic analyses, synergistic interactions were observed between the 4th quartile of three air pollutants (NO, NO, and PM) and genetic risk.
IMPACT STATEMENT
Our study for the first time revealed a non-linear trend for the association between air pollution and telomere length. The genetic analyses suggested synergistic interactions between air pollution and genetic risk on the air pollution-TL association. These findings may shed new light on air pollution's health effects, offer suggestions for identifying at-risk individuals, and provide hints regarding further investigation into gene-environment interactions.
背景
端粒长度（TL）是基因组衰老的生物标志物。有关 TL 与空气污染之间关联的证据并不一致。此外，遗传易感性对空气污染-TL 关联的修饰作用尚不清楚。
目的
本研究旨在评估环境空气污染与 TL 的关联，并进一步评估遗传易感性的修饰作用。
方法
本研究纳入了 UK Biobank 中具有完整 TL 和空气污染物数据的 433535 名参与者。应用土地利用回归模型来估计每年的平均 NO、NO、PM 和 PM 暴露水平。使用报告的与端粒相关的 SNPs 构建遗传风险评分（GRS）。通过定量聚合酶链反应（qPCR）测量白细胞 TL。采用多变量线性回归模型进行关联分析。
结果
分类暴露模型和 RCS 模型均表明，空气污染与 TL 之间存在 U 型（NO 和 NO）和 L 型（PM 和 PM）关联。与最低四分位数相比，NO 的第 2 和第 3 四分位数（q2：-1.3%[-2.1%，-0.4%]；q3：-1.2%[-2.0%，-0.3%]）和 NO（q2：-1.3%[-2.1%，-0.5%]；q3：-1.4%[-2.2%，-0.5%]）、PM（q2：-0.8%[-1.7%，0.0%]；q3：-1.3%[-2.2%，-0.5%]）和 PM 的第 3 四分位数（q3：-1.1%[-1.9%，-0.2%]）与 TL 呈负相关。NO 的最高四分位数与 TL 呈正相关（q4：1.0%[0.0%，2.0%]），而其他污染物的最高四分位数与 TL 之间的负相关也减弱且不再显著。在遗传分析中，三种空气污染物（NO、NO 和 PM）的第 4 四分位数与遗传风险之间存在协同交互作用。
意义
本研究首次揭示了空气污染与端粒长度之间关联的非线性趋势。遗传分析表明，空气污染与遗传风险对空气污染-TL 关联存在协同作用。这些发现可能为空气污染的健康影响提供新的视角，为识别高危个体提供建议，并为进一步研究基因-环境相互作用提供线索。
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